1日１回LAMA レベフェナシン 米国FDA認可

Theravance Biopharma and Mylan Receive FDA Approval for YUPELRI™ (revefenacin) in Adults with Chronic Obstructive Pulmonary Disease
http://newsroom.mylan.com/2018-11-09-Theravance-Biopharma-and-Mylan-Receive-FDA-Approval-for-YUPELRI-TM-revefenacin-in-Adults-with-Chronic-Obstructive-Pulmonary-Disease

JAMA誌解説
https://jamanetwork.com/journals/jama/fullarticle/2718777

２つの第３相試験、1225名の中等・重症COPDを revefenacin 88μg、175μg vs プラシーボランダム化、１２週後、FEV1の介入薬剤統計学的臨床的改善。副作用頻度の多いのは咳嗽、鼻咽頭炎、上気道感染、頭痛

Efficacy and safety of revefenacin (REV), a long-acting muscarinic antagonist for nebulization: results of replicate randomized, double-blind, placebo-controlled, parallel-group phase 3 trials in participants with moderate to very severe COPD
Gary Ferguson, Krishna K. Pudi, Gregory Feldmann, Srikanth Pendyala, Chris N. Barnes, Edmund J. Moran, Glenn Crater, Brett Haumann
European Respiratory Journal 2017 50: PA1812;
DOI: 10.1183/1393003.congress-2017.PA1812

52週間安全性トライアル 1055名 revefenacin 88μg、175μg vs プラシーボランダム化、175μg群がプラシーボ・ 88μg群に比べCOPD急性増悪減少。副事象は12週間トライアルと同様口腔内乾燥頻度はrevefenacin群で少ない

Revefenacin, a Once-Daily, Long-Acting Muscarinic Antagonist for Nebulized Therapy of Chronic Obstructive Pulmonary Disease (COPD): Results of a 52-Week Safety and Tolerability Phase 3 Trial in Participants with Moderate to Very Severe COPD
E.M. Kerwin,  et al.
ATS Conferences　ATS 2018　　B102. CLINICAL TRIALS AND STUDIES IN COPD

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日本で治験されてない？

ネブライザーのみ可能な症例って結構多いと思うのだけど・・・マーケット形成できないのだろうか？

米国AASLD非アルコール性脂肪肝ガイドライン総説

American Association for the Study of Liver Diseasesのガイドライン

The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases

Naga Chalasani  Zobair Younossi  Joel E. Lavine  Michael Charlton  Kenneth Cusi  Mary Rinella Stephen A. Harrison  Elizabeth M. Brunt  Arun J. Sanyal
First published: 17 July 2017 https://doi.org/10.1002/hep.29367 Cited by: 194
https://aasldpubs.onlinelibrary.wiley.com/doi/full/10.1002/hep.29367

これの解説だが結局判明したこと少なすぎて曖昧な部分が多い
コーヒー摂取のメリット、GLP-1アゴニスト、オベチコール酸、エラフィブラノールなどを含め様々な治療薬物のベネフィット検討されている
脂肪肝と肝線維化同定するためのより正確なバイオマーカーを待ち望んでいるがNICEでは候補あるも米国内で確立していない




JAMA Clinical Guidelines Synopsis　December 18, 2018
Diagnosis and Management of Nonalcoholic Fatty Liver Disease
Sonali Paul, et al.
JAMA. 2018;320(23):2474-2475. doi:10.1001/jama.2018.17365


AJOR RECOMMENDATIONS
• Patients with incidental hepatic steatosis detected on imaging who lack any liver-related symptoms or signs and have normal liver biochemistries should be assessed for metabolic risk factors (eg, obesity, diabetes mellitus, dyslipidemia) and other causes of hepatic steatosis, including alcohol consumption (>14 drinks per week for women; >21 drinks per week for men) and medications. ;肝臓関連徴候症状がなく、正常な肝生化学所見の場合、メタボリックリスク要素（e.g. 肥満、糖尿病、脂質異常）や他の脂肪肝原因（アルコール摂取：週間　女性１４ドリンク、男性 21ドリンクを超す場合、薬剤使用）を評価すべき

• Routine screening for NAFLD in high-risk groups is not advised because of uncertainties surrounding diagnostic tests and treatment options, along with lack of knowledge about long-term benefits and cost-effectiveness of screening.；高リスク群のNAFLDルーチンスクリーニングは助言せず、診断検査・治療オプションの正確性欠如のため、そして、スクリーニング長期ベネフィット・コスト効果についての知識欠如故

• The FIB-4 (age, aspartate aminotransferase, alanine aminotransferase, platelets) and NAFLD Fibrosis Score (NFS, which adds body mass index and albumin) are clinically useful tools to predict bridging fibrosis.；FIB-4(年齢、AST、ALT、血小板）とNAFLD Fibrosis Score((NFS, BMIとアルブミンを追加した指標）はbridging fibrosisの臨床的有用なツールである

• Vibration-controlled transient elastography (VCTE) or magnetic resonance elastography (MRE) can noninvasively assess for advanced fibrosis.；超音波エラストグラフィーの一つであるVibration-controlled transient elastography(VCTE)やMREは進行期線維化の非侵襲的なアクセスとなり得る

• Weight loss generally reduces hepatic steatosis, either by hypocaloric diet alone or in conjunction with increased physical activity.；一般的には体重減少は脂肪肝を減少させ、低カロリー食単打奥や身体活動増加を組み合わせることでなされる

• Pharmacologic treatments should be limited to patients with biopsy-proven nonalcoholic steatohepatitis (NASH) and advanced fibrosis.；薬物的治療は、生検確認NASHと進行期線維化に限定すべき

• Statins can be used to treat dyslipidemia in patients with NAFLD, NASH, and compensated NASH cirrhosis.；スタチンはNAFLD、NASH、代償性NASH肝硬変患者の脂質異常治療として用いられる可能性



Related guidelines and other resources
FIB-4 score
http://gihep.com/calculators/hepatology/fibrosis-4-score/
NAFLD Fibrosis Score
http://gihep.com/calculators/hepatology/nafld-fibrosis-score/
NICE NAFLD guidelines (2016)
https://www.nice.org.uk/guidance/ng49
European NAFLD consensus guidelines (2016)
https://link.springer.com/article/10.1007%2Fs00125-016-3902-y