Therapeutic Research

2015 年に団塊の世代がすべて65 歳以上の前期高齢者になり，10 年後の2025 年には75 歳以上の後期高齢者に達し，わが国はこれまで経験したことがない超高齢化社会を迎える。高齢化に伴い増加が予想される循環器疾患をどのように予防して健康寿命を延ばすかについて，第18 回日本心臓財団メディアワークショップで行われた，東京医科大学山科 章氏の講演を紹介する。

Basal –supported oral therapy（BOT） is recommended in several guidelines as initial insulin therapy in patients with type 2 diabetes mellitus. Titration of the basal insulin dose is indispensable for successful glycemic control, and main medical societies in the world recommended that dose adjustment to be done every few days, but adequate titration has not been achieved in real world settings in Japan. Without timely titration, the advantages of BOT（i.e., simple and convenient method with good treatment efficacy） are diminished. Experience of hypoglycemia may affect the attitude/behavior of patients to insulin treatment. Starting with a relatively low dose that does not trigger hypoglycemia helps to reassure patients who are anxious about insulin therapy. In this regard, however, timely titration is essential to achieve the target glycemic level. A basal insulin dose with a better profile compared with presently available ones, an algorithm for titration of the basal insulin dose, and support for patients/hospital staff are important to promote timely initiation and titration in everyday clinical settings.

Background：Diuretics cause fewer side effects when administered at low doses and exert synergistic antihypertensive activity in combination with other antihypertensive agents. We investigated the ef ficacy and safety of a combination drug containing candesartan（8 mg） and low dose of hydrochlorothiazide（6.25 mg）（candesartan/HCTZ）in daily medical practice. Methods：A prospective, multicenter, observational study was conducted by 263 medical practitioners using our hospital as the core institution. Patients receiving antihypertensive therapy that included an angiotensin II receptor blocker（ARB） who had not achieved the target clinical blood pressure were switched to candesartan/HCTZ. The primary end– point was the changes of blood pressure and pulse rate. Secondary end– points included adverse events, cardiovascular events, and changes of laboratory test results. Results：One hundred sixteen patients（mean age: 69±11 years; 64 men［55％］） were analyzed and 24 patients dropped out. Major adverse events included hypotension in 4 patients and skin rash in 3 patients. At 6 months, the systolic and diastolic blood pressures were reduced by 20±20 mmHg and 9±12 mmHg（both p＜0.0001）, respectively, while the change of pulse rate was minimal. The target blood pressure was achieved at6 months in 33 patients（35％）. Logistic regression analysis revealed that concomitant diabetes mellitus, chronic kidney disease, dyslipidemia, and a higher baseline diastolic blood pressure were significantly related to not achieving the target blood pressure. Conclusions：In patients with hypertension poorly controlled by ARB– based antihypertensive therapy, candesartan/HCTZ showed a rapid and strong antihypertensive effect that was not influenced by associated cardiovascular risk factors. Candesartan/HCTZ is an effective second – line antihypertensive agent.

目的：高度脈管侵襲を伴う切除不能進行肝細胞癌に対するsorafenib＋cisplatin分割肝動注併用療法の安全性・有効性を検証するため第1/2相臨床試験を行った。方法：第1 相試験で本治療の用量制限毒性および推奨用量を同定し，第2 相試験で推奨用量を用いて奏効率を検証した。結果：第1相試験で15例登録され，sorafenib800mg＋cisplatin 20mg/m2 で2例の用量制限毒性を認め，sorafenib 400mg＋cisplatin 30 mg/m2 を推奨用量として設定した。第2 相試験で35例登録され，推奨用量で本治療を行った結果，PR：9例，SD：18例，PD：8例，奏効率25.7％，病態制御率77.1％であり，PR 9 例のうち3 例は切除可能へconversionが認められ根治肝切除を施行しえた。結語：切除不能進行肝癌に対するsorafenib＋cisplatin分割肝動注併用療法は安全に施行可能で有効性の期待できる治療法と考えられた。

目的：気管支喘息患者を対象として，フルチカゾンフランカルボン酸エステル・ビランテロールトリフェニル酢酸塩配合剤（レルベア®エリプタ®）の使用実態下における安全性と有効性の検討を目的に，使用成績調査を実施した。方法：気管支喘息と診断され本剤を初めて投与された患者を対象とし，観察期間は本剤投与開始から12 週間とした。安全性評価は副作用の発現状況，有効性評価は，調査担当医師による総合評価，喘息コントロールテスト（ACT）スコアの変化とした。結果：本調査における安全性解析対象症例835例中42例（5.0％）に副作用が認められ，主な副作用は発声障害16例（1.9％），口腔カンジダ症8 例（1.0％），口内炎および動悸が各3 例（0.4％）であった。有効性解析対象症例740 例における総合評価での有効率は94.6％（700/740 例）であった。観察期間終了時の投与開始時からのACTスコアの変化量は5.1±4.5（平均値±SD）で，臨床的に意味のある改善とされる，スコアの変化量が3以上の患者の割合は74.3％であった。結論：本調査の結果より，わが国における本剤の使用実態下での安全性および有効性が示唆された。

Objective：This special investigation was conducted under the actual status of the usage to evaluate safety and efficacy of epoetin kappa（Epoetin alfa BS Inj. “JCR”，JCR Pharmaceuticals Co., Ltd., Ashiya）, the first biosimilar product; approved in Japan for renal anemia patients on hemodialysis. Methods：The renal anemia patients on hemodialysis treated with epoetin kappa from October 2010 to December 2011 were observed for 80 weeks or until dropout. Informed consent was obtained from all patients observed. Results：Of the 570 patients evaluated for safety, 6.84％ of patients （39 patients, 75events） experienced adverse drug reactions（ ADRs）. The major ADRs（ more than 0.50％） include bronchitis, blood pressure increased, shunt occlusion （four events, respectively）, nasopharyngitis, hypertension（ three events, respectively）. The incidence of serious ADRs was 2.28％ （13 patients, 18 events）. Of the 548 patients evaluated for efficacy,76.8％ of patients were evaluated as effective by the doctors at the point of final evaluation. Conclusions：As a result of this special investigation with renal anemia patients on hemodialysis, epoetin kappa was confirmed to be safe and effective as the innovator drug, epoetin alfa.