臨床薬理
Online ISSN : 1882-8272
Print ISSN : 0388-1601
ISSN-L : 0388-1601
44 巻, 1 号
選択された号の論文の8件中1~8を表示しています
特集/関節リウマチ治療における分子標的薬の進歩
  • 川合 眞一
    2013 年 44 巻 1 号 p. 1-2
    発行日: 2013/01/31
    公開日: 2013/02/20
    ジャーナル 認証あり
  • 亀田 秀人
    2013 年 44 巻 1 号 p. 3-7
    発行日: 2013/01/31
    公開日: 2013/02/20
    ジャーナル 認証あり
    Five biological agents against tumor necrosis factor (TNF) are now available for the treatment of rheumatoid arthritis (RA). Although the structures and the modes of administration are different among the agents, combination therapy of any anti-TNF agent and methotrexate has successfully induced clinical and morphological remission in a considerable proportion of patients with RA. Importantly, patients showing an inadequate response to one anti-TNF biological agent may respond well to another anti-TNF agent. Therefore, recent international recommendations suggest that anti-TNF agent may be both the first and the second biological agent for RA patients refractory to synthetic disease-modifying antirheumatic drugs such as methotrexate. However, the optimal use of those agents in terms of efficacy, safety and costs remains to be determined. (Jpn J Clin Pharmacol Ther 2013; 44(1): 3-7)
  • 西本 憲弘
    2013 年 44 巻 1 号 p. 9-14
    発行日: 2013/01/31
    公開日: 2013/02/20
    ジャーナル 認証あり
    Interleukin-6 (IL-6) is a multifunctional cytokine that regulates immune responses and inflammatory reactions. Deregulated over-production of IL-6 plays pathological roles in rheumatoid arthritis (RA). Therefore, blocking IL-6 actions can be a treatment for this disease. Tocilizumab is a humanized anti-human IL-6 receptor antibody and has just become available worldwide. Tocilizumab specifically blocks IL-6 binding to both membrane-bound and soluble forms of IL-6 receptor, and inhibits IL-6 signal transduction. Tocilizumab, both as monotherapy and in combination with methotrexate (MTX), has been shown to be effective in patients with RA refractory to MTX or other disease-modifying anti-rheumatic drugs. Tocilizumab also has therapeutic benefit in patients who are refractory to tumor necrosis factor inhibitors. Moreover, tocilizumab retards the progression of structural joint damage. The safety profile of tocilizumab is acceptable based on a large registry data. The agent is now approved in more than 100 countries. (Jpn J Clin Pharmacol Ther 2013; 44(1): 9-14)
  • 小池 竜司
    2013 年 44 巻 1 号 p. 15-21
    発行日: 2013/01/31
    公開日: 2013/02/20
    ジャーナル 認証あり
    Rheumatoid arthritis (RA) is a chronic polyarthritis driven by autoimmune inflammatory processes involving various factors and molecules. Not only humoral factors but cellular surface antigens can be promising targets for regulation of the disease. Rituximab (RTX) and abatacept (ABT) are drugs targeting cellular surface antigens that are now available for the treatment of RA. RTX is partially humanized chimeric anti-CD20 antibody, which was developed for the treatment of B cell lymphoma. The efficacy of RTX when added on methotrexate (MTX) for the treatment of RA was confirmed by the DANCER trial. RTX is now established as a second-line biologic drug in RA treatment guidelines in EU and US because of the effectiveness proven by the REFLEX trial. Unfortunately, RTX is not approved in Japan, and clinical trials of ocrelizumab and ofatumumab, newly developed anti-CD20 antibodies, had failed because of safety issues. ABT is a chimeric protein that combines the extracellular domain of CTLA-4 and the Fc portion of IgG1. CTLA-4 is a surface molecule expressed on T cell and is a negative regulator of the interaction between T cells and antigen presenting cells. CTLA-4 or ABT competitively inhibits CD28-CD80/86 interaction, which is an essential co-stimulatory pathway of T cell activation, and induces an anergic state in T cells. The effectiveness of ABT for biologics-naïve RA and tumor necrosis factor (TNF) antagonist-refractory RA were confirmed by the AIM trial and the ATTAIN trial, respectively. ABT is now available globally and is established as a therapeutic option for RA treatment also in Japan. (Jpn J Clin Pharmacol Ther 2013; 44(1): 15-21)
  • 山岡 邦宏, 齋藤 和義, 田中 良哉
    2013 年 44 巻 1 号 p. 23-27
    発行日: 2013/01/31
    公開日: 2013/02/20
    ジャーナル 認証あり
    Biologics targeting TNF-α and IL-6 have dramatically changed the treatment of rheumatoid arthritis (RA). Previously the therapeutic aim was to control the symptoms of arthritis. However, today our treatment goal is to achieve remission. Inflammatory cytokines involved in the pathology of RA activate multiple signaling pathways in the cytoplasm. Hence, regulating these intracellular signaling pathways has been expected to achieve similar treatment effects as biologics on RA. Recent clinical trials with compounds targeting Janus kinase (JAK) or spleen tyrosine kinase (Syk) have demonstrated high clinical efficacy resembling the biologics. Here we overview the development process of these inhibitors together with the results of clinical trials. (Jpn J Clin Pharmacol Ther 2013; 44(1): 23-27)
原著
  • Masayuki HASHIGUCHI, Eriko WATANABE, Takeshi CHIYODA, Shin IRIE, Tatsu ...
    2013 年 44 巻 1 号 p. 29-36
    発行日: 2013/01/31
    公開日: 2013/02/20
    ジャーナル 認証あり
    Background: Lifestyle-related diseases are increasing in Japan, and the national medical expenditure is increasing. Converting prescription drugs to over-the-ounter (OTC) drugs would appear to be one solution to cut expenditure. The willingness to pay (WTP) of the Japanese public for OTC imidapril, an angiotensin-converting enzyme (ACE) inhibitor, as a healthcare-related item has not been evaluated.
    Objective: To measure the value of OTC imidapril as a health care-related item by investigating the public's WTP as self-medication for primary prevention of stroke, assuming that ACE inhibitors are switched from prescription-only to OTC status.
    Methods: A questionnaire was distributed among healthy individuals engaged in various jobs in office buildings (including a clinic) in Tokyo and Fukuoka, Japan. For the WTP question format, the double-bound dichotomous choice approach was employed. Participants were randomly assigned to 3 groups. Group A was provided with a starting price per month of ¥6,000, group B with ¥8,000, and group C with ¥10,000. Weibull regression analysis was used to investigate factors affecting WTP.
    Results: The questionnaire survey was completed correctly by 311 individuals (156 men, mean age 50 years), and the mean WTP was ¥7,237 per month. Weibull regression analysis showed that gender significantly affected WTP. The bid acceptance rates differed among the age groups of 20-39 years, 40-64 years, and ≥65 years.
    Conclusion: The public's WTP amount was approximately ¥7,000 per month, and the WTP based on the questionnaire responses was about 20% lower than the present cost for physician visits. (Jpn J Clin Pharmacol Ther 2013; 44(1): 29-36)
  • 難波 志穂子, 川上 恭弘, 西原 茂樹, 千堂 年昭
    2013 年 44 巻 1 号 p. 37-46
    発行日: 2013/01/31
    公開日: 2013/02/20
    ジャーナル 認証あり
    The work of clinical research coordinators (CRCs) is extremely important and requires both interpersonal skills and high expertise. While the work is rewarding, it can also produce significant tension and burden. The stress felt by CRCs has not been reliably investigated in previous studies, and stress scales specific for this occupational category do not exist. Therefore, we designed a tool for CRC stress measurement (CRC stress management scale) to better discern the mental health status of CRCs and to standardize the measurement of stress levels in this group. In this study, the stress scale, an attribute investigation form, and the Japanese version of self-rating depression scale (SDS) were distributed to participating CRCs, and 288 responses were obtained (representing a 57.6% recovery rate). Five factors were extracted from the newly created 50-item stress scale by exploratory factor analysis. All the identified factors had α of 0.75 and above. The questions constituting each factor displayed a reasonable internal consistency. Furthermore, scores on the CRC stress scale and the Japanese version of SDS showed a positive correlation. In conclusion, the CRC stress management scale was found to be useful for the analysis of mental health specifically related to CRCs. (Jpn J Clin Pharmacol Ther 2013; 44(1): 37-46)
フォーラム
  • ―リモート SDV アンケート調査結果―
    山谷 明正, 井上 和紀, 望月 恭子, 森 奈海子, 笹浪 和秀, 肥田木 康彦, 安永 昇司, 北川 雅一, 榎本 有希子, 氏原 淳
    2013 年 44 巻 1 号 p. 47-52
    発行日: 2013/01/31
    公開日: 2013/02/20
    ジャーナル 認証あり
    Background: We conducted a questionnaire survey on clinical research associates (CRAs) of pharmaceutical companies and contract research organizations (CROs) to investigate the current status of using remote source data verification (SDV) in Japan, and to evaluate the problems related to remote SDV.
    Methods: The survey was performed using a self-administered questionnaire posed on the web site for CRAs in Japan. The questionnaire survey was carried out from 11 to 25 October 2011.
    Results: There were 640 responses from CRAs. Sixty-four percent of all respondents knew about remote SDV, and 33 CRAs had experienced using remote SDV. Regarding the possibility of using remote SDV in on-the-job training (OJT), 82% of inexperienced CRAs and 76% of experienced CRA responded “possible”. In terms of the expectation of remote SDV, 91% of experienced CRAs and 86% of inexperienced CRAs responded that they would like to use remote SDV. Although the expectation is high, 76% of CRAs responded that the standard operating procedure (SOP) describing the use of remote SDV was not available in their companies or CROs. The interval of site visit had extended significantly in sites implementing remote SDV compared with visits made by inexperienced CRAs in sites implementing standard SDV (p<0.001).
    Conclusions: The present survey showed that although remote SDV has not yet been widely implemented, there is high expectation of using remote SDV among the CRAs.The result also suggested that using remote SDV might decrease the time spent onsite and the frequency of onsite visits. The survey also showed that SOP for remote SDV is not available in many pharmaceutical companies and CROs. Guidelines and SOPs have to be established in the near future. (Jpn J Clin Pharmacol Ther 2013; 44(1): 47-52)
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