Efficacy and safety of ropeginterferon alfa-2b in Japanese patients with polycythemia vera: an open-label, single-arm, phase 2 study.

Ropeginterferon alfa-2b is a novel, site-selective, monopegylated recombinant human interferon alfa-2b. Safety and efficacy of ropeginterferon alfa-2b for the treatment of polycythemia vera were demonstrated in clinical studies conducted in European countries, but clinical studies in Japanese patients are lacking. This phase 2, open-label, multicenter, single-arm study investigated the safety and efficacy of ropeginterferon alfa-2b in 29 Japanese patients with polycythemia vera including young patients and patients with low thrombosis risk who are difficult to receive guideline-based standard treatments. The primary outcome of durable complete hematologic response without phlebotomy at months 9 and 12 was achieved by 8/29 (27.6%) patients. The fastest complete hematologic response was observed at week 12. A corresponding reduction in the JAK2 V617F allele burden from baseline to 52 weeks was also observed (mean ± standard deviation = - 19.2% ± 22.6%). No new safety concerns were identified in Japanese patients when compared with previous studies of ropeginterferon alfa-2b in European populations; the most common treatment-related adverse events were alopecia (55.2%), fatigue (27.6%) and influenza-like illness (27.6%). Most treatment-related adverse events were mild or moderate, with none of grade ≥ 3. Ropeginterferon alfa-2b is a safe and efficacious treatment option in Japanese patients with polycythemia vera.

Impaired psychomotor vigilance associated with sleep-disordered breathing in women working in the care of older adults in Japan.

PURPOSE: With a rapidly aging society, there is increasing interest in the health of female workers in the field of care services for older adults due to increasing demands to maintain 24-h care and to support older adults without errors or accidents. Therefore, the purpose of this cross-sectional study was to examine the association between sleep-disordered breathing (SDB) and sustained attention in women caring for older adults in Japan. METHODS: The study was conducted in women aged 18-67 years old working in care service facilities for older adults in Japan. The sustained attention of participants was measured by the 10-min psychomotor vigilance task (PVT). SDB was assessed based on the respiratory disturbance index (RDI), which was measured using an ambulatory airflow monitor with a polyvinylidene fluoride (PVDF) film sensor to monitor the respiratory airflow of nasal and oral breathing. The participants wore the monitor to record the breathing status while asleep at home. The severity of SDB was categorized as follows: normal, RDI < 5 events/h; mild SDB, RDI 5-10 events/h; and moderate-to-severe SDB, RDI ≥ 10 events/h. RESULTS: Of 688 women enrolled, medians of age, body mass index (BMI), sleep duration, and prevalence of hypertension tended to be higher with increasing RDI. No significant association was found between RDI and PVT parameters. However, when we limited the analysis to women with BMI ≥ 22 kg/m2, those with moderate-to-severe SDB had significantly higher odds of having the slowest 10% reaction times compared to those without SDB (OR = 2.03; 95% CI = 1.17-3.53). The association did not decrease after adjusting to account for sleep duration, alcohol drinking habits, and history of hypertension (OR = 1.97; 95% CI = 1.10-3.52). A significant increasing trend was also found between RDI and the slowest 10% of reaction times (p for trend = 0.03). CONCLUSIONS: Our findings suggest that SDB is associated with reduced sustained attention in participants with BMI ≥ 22 kg/m2, although the number of assessments of SDB and PVT was only once per participant due to the nature of the cross-sectional study.

Pharmacokinetics and Pharmacodynamics of Ropeginterferon Alfa-2b in Healthy Japanese and Caucasian Subjects After Single Subcutaneous Administration.

BACKGROUND AND OBJECTIVES: Ropeginterferon alfa-2b is a novel monopegylated recombinant interferon alfa-2b for the treatment of patients with polycythemia vera. The objectives of this study were to evaluate the pharmacokinetics, pharmacodynamics, safety, and tolerability of ropeginterferon alfa-2b in healthy Japanese subjects compared with Caucasian subjects. METHODS: In this multicenter, parallel-group phase I study, a cohort consisting of six Japanese and six Caucasian subjects was designated to receive a single subcutaneous dose of ropeginterferon alfa-2b (100, 200, 300, and 450 µg). Pharmacokinetic and pharmacodynamic parameters, and immunogenicity were evaluated. Safety was assessed throughout the study. RESULTS: Cohort 4 (450-µg dose) was not initiated because the primary objective of this study was achieved based on the three completed cohorts. A total of 36 enrolled subjects (18 Japanese and 18 Caucasian) in three cohorts were included in the safety, pharmacokinetic, and pharmacodynamic analysis sets. Ropeginterferon alfa-2b exposure in terms of the area under the serum concentration-time curve (AUC) from time zero extrapolated to infinity and the AUC from time zero to the time of the last quantifiable concentration was approximately 1.7-fold and two-fold higher in Japanese subjects than in Caucasian subjects, respectively. Across the same dose range, the maximum serum concentration was approximately 1.25-fold higher in Japanese subjects than in Caucasian subjects. The time to reach the median maximum serum concentration was similar between ethnicities (approximately 96-111 h). The terminal half-life was 48-57 h in Japanese subjects and 31-75 h in Caucasian subjects. The slope of the relationship between dose and drug exposure was greater than 1 in both ethnicities. The dose-dependent induction of beta-2 microglobulin and neopterin expression was observed in both ethnicities, and the two groups showed similar pharmacodynamic parameters. At the end of the study, 22.2% of Japanese subjects and 11.1% of Caucasian subjects developed anti-ropeginterferon alfa-2b-binding antibodies. The neutralizing capacity of these antibodies was not tested. Ropeginterferon alfa-2b up to 300 µg was safe and well tolerated, with no unexpected safety findings based on previous experiences with ropeginterferon alfa-2b and other forms of interferon. CONCLUSIONS: Ropeginterferon alfa-2b exposure was higher in Japanese subjects than in Caucasian subjects. The increase in ropeginterferon alfa-2b exposure was greater than the dose proportion in the dose range of 100-300 µg. Ropeginterferon alfa-2b was safe and well tolerated. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT03546465, registered on 6 June, 2018.

Proposal of Standard for Medical Science Liaison (MSL) Profession in Japan: A Viewpoint from the Japanese Association of Pharmaceutical Medicine (JAPhMed).

Medical science liaisons (MSLs) are field-based professionals sited in medical affairs (MA) departments who contribute to the generation of medical evidence and exchange advanced medical and scientific information with healthcare professionals to standardize treatments and maximize the value of medical products for patient outcomes. As such, it is essential for companies to have MSL training programs that cover areas such as advanced scientific expertise, pharmaceutical regulations, and medical communication proficiency and to certify the knowledge and skills that enable MSLs to perform their tasks effectively. The lack of a standardized training curriculum, assessment of MSL capabilities, and key performance indicators (KPIs) in Japan has made it difficult for MSLs to carry out these tasks. It is important to clarify the status of MSLs in MA divisions within the Japanese pharmaceutical industry. The mission of the Japanese Association of Pharmaceutical Medicine (JAPhMed) is to promote pharmaceutical medicine by enhancing the knowledge, expertise, and skills of pharmaceutical professionals. JAPhMed established an accreditation system for the MSL certification programs of individual companies in early 2015 and then embarked on defining the individual MSL qualifications from late 2015 to mid-2017. Here, we describe the MSL recommendation that covers (1) MA in Japan, (2) definition of MSL, (3) roles and activities of MSLs, (4) regulation and compliance for MSLs, (5) qualification requirements for MSLs, (6) KPIs for MSLs, and (7) a training curriculum for MSLs. In the training curriculum, JAPhMed considered the relevance of each part of the training curriculum in terms of the fixed roles and activities of MSLs.

Prevalence of sleep-disordered breathing among women working in the aged care services in Japan.

OBJECTIVES: The aim of this study was to examine the prevalence of sleep-disordered breathing (SDB) in women working in the field of aged care in Japan. METHODS: A cross-sectional study was conducted for female employees aged 18-60 years in aged care facilities in Japan. The analyzed set consisted of 712 participants with complete data. SDB was determined by respiratory disturbance index (RDI), measured using an ambulatory airflow monitor with a polyvinylidene fluoride film sensor to detect nasal and oral airflow overnight at home. Based on the findings of previous studies, RDI 10 was considered equivalent to apnea-hypopnea index (AHI) 15. RESULTS: The prevalence of moderate-to-severe SDB (RDI ≥ 10) was 22.8%. The mean age was 38.1 years, and mean sleeping time of participants was 6.1 h. The median body mass index (BMI) was 22.0. Women with moderate-to-severe SDB (RDI ≥ 10) had a higher age, neck circumference, neck-height ratio, BMI, systolic blood pressure, and increased prevalence of hypertension, short sleepers (amount of sleep on the SDB testing day < 6 h), and habitual snorers, compared to women with no or mild SDB (RDI < 10). CONCLUSIONS: Our study found that women working in the aged care services in Japan were heavily burdened by SDB even though they were relatively young and slim. To prevent CVD from developing in the future, programs through which workplaces can help their employees improve their lifestyle, and early diagnosis and treatment of SDB are highly recommended.