Therapeutic Research

Background：Topiroxostat, a selective xanthine oxidoreductase inhibitor, is used for the management of hyperuricemia in patients with or without gout in Japan. Topiroxostat effectively reduced serum uric acid levels in patients with hyperuricemic stage 3 chronic kidney disease in clinical trials. However, the safety and efficacy of topiroxostat in the real clinical setting remain unclear, and there is little large‒scale clinical evidence. We are currently conducting a postmarketing observational study during an observation period of 54 weeks. Object：To assess the safety and efficacy of topiroxostat in clinical practice, as the number of cases observed during an 18‒week period has exceeded 2000. Methods：Patients were centrally enrolled, and case report forms of 2104 patients were collected between April 2014 and June 2016 from 796 medical sites. Safety and efficacy were evaluated by the physicians in charge at each site. Adverse events and adverse drug reactions were coded according to the Medical Dictionary for Regulatory Activities. Results：The incidence of adverse drug reactions was 4.38％（89/2033 cases）based on our safety analysis. The main adverse drug reactions were gouty arthritis in 12 cases （0.59％）, abnormal hepatic function in 11 cases（0.54％）, renal impairment in 7 cases （0.34％）, liver disorder in 5 cases（0.25％）, and rash in 5 cases（0.25％）. Among the 1978 subjects for effectiveness analysis, the average rates of reduction of serum uric acid levels at 18 and 54 weeks after the administration of topiroxostat were 18.72％ and 21.16％, respectively. The average rates for subjects who achieved serum uric acid levels≦6.0 mg/dL at 18 and 54 weeks after administration were 43.42％ and 51.68％, respectively. Conclusion：This interim report suggests that there is no particular concern about adverse drug reactions and efficacy of topiroxostat for hyperuricemic patients with or without gout in postmarketing settings in Japan.

Objectives：Research studies based on International Clinical Trial Registry Platform （ICTRP） data include a number of systematic reviews or meta‒analyses focused on specific diseases, but only a few studies have analyzed the trends in clinical trials across countries. We aimed to clarify the study characteristics of countries that have not been the focus of the previous reports. The differences between the countries in terms of the ratios of interventional studies to observational studies, gender and ages of the subjects, and trial phases were analyzed. Methods：The present cross‒sectional study used registered data from clinical trials. All data from clinical trials registered from January 1, 2012 to December 31, 2014 were downloaded from the WHO’s ICTRP search portal on January 13, 2016 and analyzed. Cross tabulation of the clinical trial data based on the country, registry, gender, study type, etc. was performed, and a chi‒squared test of independence was conducted to find the differences between the countries. Results：From the adjusted standardized residuals of the chi‒squared test of independence, it was seen that relatively many interventional studies were conducted in the United States, the United Kingdom, and Australia/New Zealand. A relatively large number of clinical trials were conducted on female subjects in the United States, Italy, and China, and many clinical trials were conducted on male subjects in the United Kingdom, the Netherlands, Germany, and Australia/New Zealand. Clinical trials in Japan and India were conducted on both male and female subjects. Conclusions：The contents of the clinical trials are receiving the social background, law, and other effects of the country. In countries that have traditionally developed clinical epidemiology expertise, biostatistics and a social infrastructure that supports clinical trials has been established；the proportion of intervention studies are high. In countries where many new drugs for conditions such as cervical cancer and breast cancer are developed, a high percentage of clinical studies target women.

This study examined changes in attitudes toward life in patients who participated in the Chronic Disease Self‒Management Program（CDSMP）, which was a workshop held in Japan to help patients with chronic diseases to manage their lives themselves. Patients who had participated in the CDSMP between June 2010 and October 2013 completed a follow‒up questionnaire survey 3 months after their original participation. Responses were obtained from 338 participants. Approximately 80％ of participants provided affirmative responses to“I am not the only person who has a difficult time” and“ I do not have to rush or push myself too far”, and between 60％ and 70％ provided affirmative responses to“ My life feels easier than it did before”and“I am now able to accept my disease”. This suggests that the CDSMP helped patients with various chronic diseases to share their experiences, eliminate their worries, and adopt positive attitudes toward their lives. In addition, it is important that patients with chronic diseases interact with each other.