坂東 政司

A randomised, double-blind, phase II, dose escalation trial was conducted to assess the safety, tolerability and pharmacokinetics of the tyrosine kinase inhibitor nintedanib, alone and when added to ongoing pirfenidone therapy, in Japanese patients with idiopathic pulmonary fibrosis. 50 Japanese patients were randomised to receive nintedanib or placebo in one of three cohorts (nintedanib 50 mg twice daily or 100 mg twice daily for 14 days, or 150 mg twice daily for 28 days). Patients receiving pirfenidone at inclusion were stratified to every nintedanib dose group and placebo. Adverse events were reported in nine out of 17 patients receiving nintedanib alone and 10 out of 21 patients receiving nintedanib added to pirfenidone. All adverse events were mild or moderate in intensity. Gastrointestinal disorders were the most common adverse event Maximum plasma concentration and area under the curve at steady state for nintedanib and its metabolites tended to be lower when nintedanib was added to pirfenidone. Nintedanib had no effect on the pharmacokinetics of pirfenidone. In conclusion, further study is needed to evaluate the safety and tolerability profile of nintedanib when added to pirfenidone in patients with idiopathic pulmonary fibrosis. There was a trend toward lower exposure of nintedanib when it was added to pirfenidone.

Background: There have been no prospective large-scale multicenter epidemiological studies on the clinical course and treatment from the time of diagnosis of idiopathic interstitial pneumonias (IIPs) in Japan. The purpose of this study was to clarify the current clinical situation of IIP in Japan. Methods: This study was supported by a grant from the Ministry of Health, Labour and Welfare to the Diffuse Lung Diseases Research Group. Data including clinical findings, course, and treatment of IIP from a web database created by a collaborative effort of medical institutions across Japan that specialize in the care of interstitial pneumonias were collected and analyzed. Results: A total of 436 IIP patients from 19 institutions were newly registered during a 5-year period. Idiopathic pulmonary fibrosis (IPF) was the most frequently encountered IIP, and 28% of the IPF cases were initially diagnosed by abnormal chest X-ray or CT in asymptomatic patients. Until the 2008 fiscal year, no treatment was given for most cases of IPF. After the end of 2008, when pirfenidone was approved for manufacture, the number of patients for whom no treatment was recommended declined, and pirfenidone therapy was initiated in 32.9% of cases in 2009. The median survival times for IPF from the onset symptoms and from the initial visit were 105 months and 69 months, respectively. Conclusions: This study should provide valuable information for understanding the current state of IIP in Japan.

Background: National surveys conducted in Japan between 1960 and 2004 suggest a gradually increasing incidence of sarcoidosis in women >50 years old with increased involvement of the eye, skin, and heart. However, whether this involvement is due to the increased age at diagnosis is still unclear. We aimed here to identify the age-related differences in organ involvement in sarcoidosis in Japan, as well as the historical changes in clinical characteristics and the age-specific distribution of cases at diagnosis. Methods: We reviewed 588 consecutive Japanese patients newly diagnosed with sarcoidosis between 1974 and 2012 at Jichi Medical University Hospital. We compared organ involvement between subgroups differentiated by sex and age (<45 years; n = 275; >= 45 years; n = 313) at diagnosis and identified historical changes in the age-specific distribution in 10-year intervals. Results: Younger patients had more common involvement of extrathoracic lymph nodes, parotid/salivary gland, and liver, while older patients had more common involvement of nonlymphatic extrathoracic organs such as the eye, heart, muscle, and kidney. The age at diagnosis has consistently increased over the past four decades. The monophasic distribution in men has tended to become biphasic, and the biphasic distribution in women monophasic. Increasing trends were apparent for hypercalcemia and involvement of the gastrointestinal tract, skin, nervous system, muscle, and kidney. Conclusions: Elderly patients at diagnosis had various extrathoracic involvement including eye, skin, and cardiac lesions. Moreover, the age at diagnosis of sarcoidosis has continued to increase in both sexes, influencing the recent trends in clinical characteristics. (C) 2015 Elsevier Ltd. All rights reserved.

Rationale: Idiopathic pulmonary fibrosis (IPF) has an unknown etiology and poor prognosis. Several large-scale epidemiologic studies have been conducted predominantly in Western countries. There are few studies reported from Asian countries. It remains unclear whether ethnic difference exists in IPF. It is important to determine the current IPF status in Asian populations and compare it with that of Western populations. Objectives: To provide the epidemiologic status of IPF in Japan and to investigate ethnic differences. Methods: We selected Hokkaido prefecture (population, 5.6 million) as the epidemiologic cohort of IPF among Japanese. On the basis of the clinical records of 553 patients with IPF who were accepted based on the application of the Certificate of Medical Benefit between 2003 and 2007, we conducted a retrospective epidemiologic and prognostic analysis. Measurements and Main Results: The prevalence and cumulative incidence of IPF was 10.0 and 2.23 per 100,000 population, respectively, with 72.7% predominance of males and an increase in frequency with age. The median survival time was 35 months, and the most common (40%) cause of death was acute exacerbation. The most important factor influencing IPF prognosis was the percent vital capacity. Conclusions: The status of IPF in the Japanese population was clarified for the first time through our study. Our results showed that in men, the incidence of death caused by acute exacerbation was higher and that caused by cardiovascular disease was lower in Japan than in Western countries. These results may suggest ethnic differences in IPF.