Therapeutic Research

第29 回国際高血圧学会が2022 年10 月12 ～ 16 日に16 年ぶりに日本で第44 回日本高血圧学会総会（10 月14 ～ 16 日，京都）と同時開催された。それに先立って10月3日に日本高血圧学会プレスセミナーで楽木宏実理事長が解説した高血圧ガイドライン策定，ステートメント，減塩・栄養関連の活動について紹介する。

心房細動アブレーション後に perimitral atrialtachycardia（PMAT）で再発する症例を経験する。左下肺静脈から僧帽弁輪にかけてのmitralisthmusを線状焼灼しblock lineを作成することが一般的に有効であるが，難渋するケースがある。特に本例のように肥大型心筋症（HCM）症例ではしばしば難渋する。近年vein of Marshall（VOM）に無水エタノールを注入するケミカルアブレーションがmitral isthmus block 作成に有用であることが報告されている。HCMを背景とした心房細動アブレーション後，PMATで再発しVOMのケミカルアブレーションが劇的に奏効した2例を経験したので報告する。

Objectives：To evaluate data on the safety and clinical outcomes of sotrovimab in patients infected with severe acute respiratory syndrome coronavirus 2（SARS‒CoV‒2） in real‒world clinical practice. 　　Methods：Included patients were infected with SARS‒CoV‒2, had risk factors for progression to severe SARS‒CoV‒2 infection, did not require oxygen therapy due to SARS‒CoV‒2 infection at baseline and received sotrovimab for the first time（target sample size：630 patients for enrollment）. The observation period was 29 days, counting the date of sotrovimab treatment as day 1. Inpatients were observed until discharge from hospital or transfer to another hospital. Outpatients were observed on day 1 only. Safety was evaluated through occurrence of adverse drug reactions（ADRs）, and ADRs related to “serious hypersensitivity such as anaphylaxis, infusion reactions”were evaluated as events of special interest. Progressor rate was evaluated as the endpoint of clinical outcomes. 　　Results：Between 31 January and 19 August 2022, 512 patients were enrolled in this study, and 346 case report forms（CRFs）were finalized. Among 346 patients in the safety analysis population, 9 patients（2.6％）experienced ADRs. The reported ADRs were “pyrexia”in 7 patients（2.0％）, and“COVID‒19 pneumonia”“, dyspnoea”“, oropharyngeal pain”, and“eczema”in 1 patient（0.3％）. Two ADRs of special interest（“dyspnoea”and “eczema”）were reported. The percentage of progressors in the 246 patients included in Authothe clinical outcome analysis population was 0.4％（1/246 patients）. Regarding the progressor rate by SARS‒CoV‒2 sampling period, 0.8％（1/118 patients）progressed to severe SARS‒CoV‒2 infection from 31 January to 27 March 2022（BA.1 dominant period）and there were no progressors to severe SARS‒CoV‒2 infection（0.0％, 0/128 patients）from 28 March to 19 June 2022（BA.2 dominant period）. 　　Conclusions：This interim report did not identify any new concerns regarding the safety and clinical outcomes of sotrovimab. The study is ongoing and will provide additional data on the real‒world safety and effectiveness of sotrovimab.

Objectives：To evaluate the safety and effectiveness of hydroxychloroquine（HCQ） in real‒world treatment of patients with lupus erythematosus, either systemic（SLE）or cutaneous（CLE）. 　　Methods：We designed a nationwide drug use‒results survey of HCQ treatment‒naïve patients with SLE or CLE under the Risk Management Plan. Safety and effectiveness data were collected for patients treated with HCQ enrolled from March 2016 to March 2018. Patient adherence to the ocular examination schedule was also reviewed. 　　Results：Of 1,181 patients, 1,142 were included in the safety analysis. ADRs developed in 209 patients（18.30％, most commonly diarrhea, rash, and drug eruption）, and 36 experienced serious ADRs（3.15％, most commonly eye disorders）. Emerging eye disorders occurred nearly constantly throughout the study, while ADRs other than emerging eye disorders occurred most frequently during the first 4 weeks after the start of HCQ administration. Skin manifestations improved at final evaluation in 49.3％ of patients（SLE 47.3％, CLE 60.0％）based on physician assessment and in 48.7％ of patients（SLE 47.3％, CLE 56.0％）based on patient impressions. Significant decreases in fatigue and in myalgia and arthralgia were noted at 52 weeks and at final evaluation, based on patient VAS（p＜ 0.0001）. Multivariable analysis showed that diagnosis, disease duration, smoking habit, and the total daily dose of oral steroid at the start of administration were significantly related to effectiveness. 　　Conclusion：This survey did not raise any new safety concerns for long‒term use. HCQ was well tolerated and effective for CLE and SLE patients in a real‒world clinical setting.

Background：In asthma treatment, the possibility of early introduction of ICS/LABA/LAMA triple‒inhaled drugs is being discussed. 　　Object：To retrospectively investigate whether ICS/LABA/LAMA triple inhalation can achieve the oral free status that does not require oral medication while improving asthma control conditions. 　　Method：Adult outpatients with stable well‒controlled moderate asthma（JGL2021standard STEP 3） who started treatment of ICS/LABA/LAMA Triple Inhalation （Trelegy® 200：FF/VI/UMEC 200）in combination of oral medications for at least 3 months were enrolled and examined retrospectively from medical records. Results：77 patients（58.8±15.4yr, male‒female ratio 28/49）were registered. The 71.4％ of patients achieved oral free status. The average time to reach oral free status was 2.8±1.5 months after the start of FF/VI/UMEC 200. The ACT score of 21.2±3.5 changed 23.1±2.3 after achieving oral free status（n＝42, p＝0.004）. The CAT score of 12.8±8.7 changed 6.9±5.5 after achieving oral free status（n＝18, p＝0.027）. The FeNO significantly improved from 38.5±35.8 ppb to 25.6±14.7 ppb after achieving oral free status（n＝40, p＝0.005）. 　　Conclusion：Continued use of ICS/LABA/LAMA triple inhalants（FF/VI/UMEC 200）may possibly achieve the condition of using inhalation therapy alone and an oral free state that does not require oral medication while significantly improving asthma control. This suggests a kind of evidence for the usefulness of early adoption of ICS/LABA/LAMA triple inhalation in asthma treatment.

背景と目的：新規尿酸排泄促進薬のドチヌラドは，eGFR 30 mL/min/1.73 m2未満の高度腎機能低下者への投与が禁忌ではなく慎重投与とされているが，実地投与の評価を行う。　対象と方法：尿酸値7.1 mg/dL 以上でeGFRが9.9～23.7 mL/min/1.73 m2のCKD 患者10 例（男7 例・女3 例，年齢75.7±14.7 歳，CKD 原疾患は慢性糸球体腎炎3 例，糖尿病4.例，腎硬化症2 例，腎移植後慢性拒絶反応1 例）について尿酸値，腎機能，肝機能を後向きに検討した。　結果：尿酸値は投与前8.62±1.80 で半年後7.34±0.93 だった（p＝0.060）が，1 年後には6.29±1.42 に有意に低下した（p＝0.013）。eGFRは投与前に18.4±4.1 だったのが，半年後に15.2±4.0 と一時的に有意に低下したが（p＝0.022），1 年後には16.7±6.7 と投与前と同水準に戻った（p＝0.265）。AST/ALT/γGTPの値には有意な変化はなく，他に有害事象は認めなかった。ドチヌラド投与量は1 年後で2.10±1.10 mg/日だった。　考察：旧世代の尿酸排泄促進薬であるベンズブロマロンとプロベネシドは高度腎機能低下に対し禁忌だが，主に肝代謝のドチヌラドは肝障害がないかぎり高度腎障害への投与は可能と考えられるも，治験段階で高度腎障害患者への投与経験がなく慎重投与とされた経緯がある。当研究は高度腎障害者へのドチヌラドの投与を可とする端緒となると思われる。　結語：ドチヌラドは慎重に投与を行うかぎり，CKD stage G4，G5 の患者の尿酸値を有効かつ安全に下げると考えられる。