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Background: To compare peramivir 300 mg single‐dose, peramivir 600 mg repeat‐dose, and oseltamivir effects on health‐related quality of life, including respiratory symptoms and general conditions, time to symptom alleviation, time to fever resolution, incidence of exacerbations, and virus titer, in influenza patients with chronic respiratory disease. Methods: We report additional outcomes from a 2‐week, multicenter, randomized, open‐label study in Japan (UMIN000030118). Influenza patients with chronic respiratory disease received intravenous peramivir (300 mg single‐dose [n = 66], 600 mg repeat‐dose [600 mg/d of 2 consecutive days; n = 70]) or oral oseltamivir (75 mg twice daily, 5 days; n = 72). The principal endpoint of this analysis was change from baseline to Day 14 at each time point in Chronic Obstructive Pulmonary Disease Assessment Test (CAT) scores. Results: Both peramivir regimens reduced total CAT score at Day 3 more than oseltamivir (peramivir 600 mg vs oseltamivir, P =.0032; peramivir 300 mg vs oseltamivir, P =.0203). Cough/phlegm CAT scores were most improved with peramivir 600 mg. Median time to alleviation of three respiratory symptoms was longer with peramivir 600 mg (68.9 hours) than with peramivir 300 mg (50.6 hours, hazard ratio [HR] 1.57; P =.0191) and shorter with peramivir 300 mg than oseltamivir (78.8 hours, HR 0.62; P =.0141). Alleviation of seven influenza symptoms and fever resolution was shortest with peramivir 300 mg. Conclusions: Rapid improvement in CAT score, including cough, and shorter time to alleviation of respiratory symptoms associated with peramivir is of potential benefit to patients with chronic respiratory disease. [ABSTRACT FROM AUTHOR]

Background: The efficacy of neuraminidase inhibitors on improvement of respiratory symptoms triggered by influenza in patients with pre‐existing chronic respiratory diseases is unknown. Methods: This 2‐week, randomized, open‐label study evaluated intravenous peramivir 600 mg on two consecutive days (peramivir‐repeat), peramivir 300 mg single dose (peramivir‐single), and oral oseltamivir 75 mg twice daily for 5 days in patients with confirmed influenza and chronic respiratory diseases. Patients recorded symptom scores daily. The primary endpoint of cumulative area of time vs symptoms (CATVS) was expressed as an index value of area under the curve vs time of the total score of cough, sore throat, and nasal congestion from baseline to 2 weeks. Results: Of 214 randomized patients, 209 (56% female, 77% aged <65 years, 94% outpatients, 91% bronchial asthma, 62% influenza A) received ≥1 dose of study drug. Mean (standard deviation) CATVS was similar for peramivir‐repeat (782.78 [487.17]) vs peramivir‐single (717.35 [347.55]; P =.4371), and for peramivir‐repeat vs oseltamivir (856.34 [404.99]; P = 1.00). However, CATVS was significantly shorter for peramivir‐single vs oseltamivir, with an estimated treatment difference (TD) of −145.07 (95% confidence interval: −284.57, −5.56; P =.0416). In subgroup analyses, CATVS was significantly shorter for peramivir‐single vs oseltamivir among patients with influenza A (TD: −206.31 [−383.86, −28.76]; P =.0231), bronchial asthma (TD: −156.57 [−300.22, −12.92]; P =.0328), baseline respiratory severity score <5 (TD: −265.32 [−470.42, −60.21]; P =.0120), and age <65 (TD: −184.30 [−345.08, −23.52]; P =.0249). Conclusions: In patients with chronic respiratory diseases, peramivir‐single was not significantly different from peramivir‐repeat and was more effective than oseltamivir at alleviating respiratory symptoms. [ABSTRACT FROM AUTHOR]

Background: Indacaterol is an investigational, novel, inhaled once-daily ultra-long-acting beta-2 agonist for the treatment of chronic obstructive pulmonary disease (COPD). This study evaluated the 24-h bronchodilatory efficacy and safety of indacaterol in Japanese patients with COPD. Methods: This Phase-II, randomised, placebo-controlled, crossover study comprised four double-blind, single-dose treatment periods (washout between periods: 14-28 days). Japanese patients aged 40-75 years with moderate-to-severe COPD were randomised to receive single doses of indacaterol (150, 300, or 600 µg) or placebo via a single-dose dry-powder inhaler. Efficacy (primary endpoint: standardised FEV1AUC22-24h) and safety were assessed for 24 h post-dose in each treatment period. Results: Of the 50 patients randomised (92% male; mean age, 67.2 years), 45 completed the study. Standardised FEV1AUC22-24h was significantly higher for all indacaterol doses as compared with placebo, with clinically relevant differences of 130, 160, and 170 mL for 150, 300, and 600 µg, respectively (P < 0.001). The improvement in FEV1 was seen as early as 5 min post-dose with indacaterol and sustained for 24 h (P < 0.001 vs placebo at all time points). All indacaterol doses were well tolerated and showed no clinically meaningful effect on pulse rate, blood pressure, QTc interval, and laboratory parameters when compared with placebo. Conclusions: In the Japanese COPD population studied, single doses of indacaterol (150, 300, and 600 µg) provided sustained 24-h bronchodilation, with onset of action within 5 min post-dose. All doses were well tolerated. These results are consistent with data from Caucasian populations. [ABSTRACT FROM AUTHOR]

Introduction: In the IMPACT trial, single-inhaler triple therapy fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) reduced moderate/severe exacerbation rates versus FF/VI or UMEC/VI dual therapy in patients with chronic obstructive pulmonary disease (COPD); however, pneumonia incidence was higher in FF-containing arms. As COPD is a growing problem in Asia, we compared the efficacy and safety of FF/UMEC/VI in Asia versus non-Asia regions. Methods: IMPACT was a double-blind, 52-week trial in symptomatic COPD patients with ≥ 1 moderate/severe exacerbation in the prior year. This pre-specified analysis evaluated the annual rate of moderate/severe exacerbations, change from baseline in trough forced expiratory volume in 1 s, and St George's Respiratory Questionnaire total score, mortality, and safety (including pneumonia) in Asia versus non-Asia regions. Results: The intent-to-treat population comprised 10,355 patients (Asia n = 1644 [16%]). Rate ratios (95% confidence intervals) for moderate/severe exacerbations with FF/UMEC/VI were 0.89 (0.76–1.05) versus FF/VI and 0.86 (0.71–1.04) versus UMEC/VI in Asia, and 0.84 (0.79–0.90) and 0.74 (0.68–0.80) in non-Asia. Efficacy of FF/UMEC/VI on other endpoints was similar in both regions. There was an increased incidence of investigator-reported pneumonia in patients in Asia (FF/UMEC/VI: 13%; FF/VI: 14%; UMEC/VI: 6%) compared with non-Asia (FF/UMEC/VI: 6%; FF/VI: 5%; UMEC/VI: 4%). The increased risk of pneumonia in patients in Asia was most marked in patients with lower body mass index, lower lung function, and taking inhaled corticosteroids. In post hoc analysis of adjudicated on-treatment all-cause mortality, probabilities of death were numerically lower in both regions with FF/UMEC/VI (Asia: 1.16%; non-Asia: 1.35%) and FF/VI (Asia: 1.77%; non-Asia: 1.21%) versus UMEC/VI (Asia: 1.91%; non-Asia: 2.23%). Conclusions: FF/UMEC/VI provides similar benefits in COPD patients in Asia and non-Asia regions. Clinical benefits of treatment, including reduction in mortality risk, should be weighed against risk of pneumonia, taking account of all known risk factors. Trial Registration: ClinicalTrials.gov identification, NCT02164513. [ABSTRACT FROM AUTHOR]

Background In the Phase III CALIMA trial, benralizumab significantly reduced asthma exacerbations, increased lung function, and alleviated symptoms for patients with severe, uncontrolled eosinophilic asthma. The aim of this subgroup analysis was to evaluate the efficacy and safety of benralizumab for Japanese patients in the CALIMA trial. Methods CALIMA was a randomised, controlled trial of 1306 patients (aged 12–75 years; registered at ClinicalTrials.gov: NCT01914757 ) with severe asthma uncontrolled by medium- to high-dosage inhaled corticosteroids and long-acting β 2 -agonists (ICS/LABA). Patients received 56 weeks' benralizumab 30 mg either every 4 weeks (Q4W) or every 8 weeks (Q8W; first three doses Q4W), or placebo Q4W. The primary analysis population was patients receiving high-dosage ICS/LABA with blood eosinophils ≥300 cells/μL. This subgroup analysis covered Japanese patients from this group. Results Of 83 patients randomised in Japan, 46 were receiving high-dosage ICS/LABA and had blood eosinophils ≥300 cells/μL. Compared with placebo, benralizumab reduced the annual rate of asthma exacerbations by 66% (Q4W; rate ratio 0.34, 95% CI, 0.11–0.99) and 83% (Q8W; rate ratio 0.17, 95% CI, 0.05–0.60); increased prebronchodilator FEV 1 by 0.334 L (Q4W; 95% CI, 0.020–0.647) and 0.198 L (Q8W; 95% CI, −0.118 to 0.514); and decreased total asthma symptom score by 0.17 (Q4W; 95% CI, −0.82 to 0.48) and 0.24 (Q8W; 95% CI, −0.87 to 0.40). Percentages of adverse events were consistent with the overall CALIMA group. Conclusions Benralizumab reduced annual asthma exacerbations and symptoms, increased lung function, and was well-tolerated by Japanese patients with severe, uncontrolled eosinophilic asthma. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: Those who have brain metastases smaller than 30mm in diameter and less than 5 in number can be treated less invasively with radiosurgery. This retrospective study evaluated the optimal brain magnetic resonance image (MRI) follow-up interval for non-small cell lung cancer (NSCLC) patients to detect radiosurgically manageable metachronous brain metastases (MBM). Patients and methods: The records of 551 patients with primary NSCLC, treated in our institute between 2002 and 2007, were reviewed. The initial brain MRI was performed within one month after diagnosis of NSCLC, and the follow-up brain MRI interval was at the discretion of physicians. The interval between the last MRI in which brain metastases were not found and the first MRI in which brain metastases were found was defined as the critical MRIs interval (CMI). The relationship between CMI and the maximum size or number of MBM was evaluated. Results: Among reviewed patients, the initial MRI of 38 patients showed brain metastases and 29 patients were diagnosed as MBM. In these MBM patients, the median interval from diagnosis of NSCLC to diagnosis of brain metastases was 8.9 months. The median CMI was 4.7 (range: 1.6–18.9) months. All brain metastases smaller than 30mm in maximum diameter were found when CMI was shorter than 6.0 months, although 5 or more brain metastases in number were detected even by shorter CMI than 3 months. Conclusion: Early detection of MBM by biannual MRI follow-up may provide NSCLC patients with more opportunities to have less invasive treatment. [ABSTRACT FROM AUTHOR]

The goal of this study was to assess the long-term safety and efficacy of mepolizumab in patients with the most severe eosinophilic asthma. This multicenter, open-label, long-term, Phase IIIb study (COSMEX [COSMOS Extension]; 201312/NCT02135692) enrolled patients from the 52-week, open-label extension study COSMOS (A Study to Determine Long-term Safety of Mepolizumab in Asthmatic Subjects) that previously enrolled patients from the double-blinded, placebo-controlled Phase III studies MENSA (Mepolizumab as Adjunctive Therapy in Patients with Severe Asthma) and SIRIUS (Steroid Reduction with Mepolizumab Study). To enter COSMEX, patients had to have life-threatening/seriously debilitating asthma before entering MENSA or SIRIUS and to have completed these previous studies with demonstrated improvement while receiving mepolizumab. In COSMEX, patients received mepolizumab 100 mg subcutaneously every 4 weeks as add-on therapy for up to 172 weeks. Primary endpoints were adverse event frequency and exacerbation rate per year; also assessed were forced expiratory volume in 1 s, Asthma Control Questionnaire-5 score, and daily oral corticosteroid (OCS) use. Of the 340 patients enrolled, 339 received mepolizumab; median treatment duration within this extension study was 2.2 years, equating to 718 patient-years of additional exposure. No new safety signals were identified. Patients receiving mepolizumab throughout this study and previous studies had lasting reductions in exacerbation rate and daily OCS use and improvements in forced expiratory volume in 1 s and Asthma Control Questionnaire-5 score. In COSMEX, the on-treatment exacerbation rate (95% CI) was 0.93 (0.81–1.06) event/year for clinically significant exacerbations, 0.13 (0.10–0.18) event/year for exacerbations requiring hospitalization/emergency department visit, and 0.07 (0.05–0.10) event/year for exacerbations requiring hospitalization. In patients requiring systemic/oral corticosteroids with ≥128 weeks of continuous enrollment across SIRIUS, COSMOS, and COSMEX, mepolizumab maintained the median daily OCS dose at 1.3–2.8 mg during COSMEX, with additional patients no longer requiring OCS after extended mepolizumab treatment. This study indicates that long-term mepolizumab treatment is well tolerated and associated with sustained clinical benefits in patients with severe eosinophilic asthma. ClinicalTrials.gov identifier: NCT02135692. [ABSTRACT FROM AUTHOR]