標的放出ブデソニドとプラセボのIgA腎不全患者 (NEFIGAN):二重盲検,ランダム化,プラセボ対照の2b期試験
Bengt C Fellström1, Jonathan Barratt2, Heather Cook3
1Uppsala University Hospital, Uppsala, Sweden.
Lancet (London, England)
|April 2, 2017
まとめ
標的放出ブデソニドは,IgA腎不全患者のタンパク質尿を有意に減少させ,末期腎疾患のリスクを低下させました. これは粘膜免疫を標的とした新たな治療法となる可能性があります.
科学分野:
- 腎臓科
- 免疫学
- 胃腸内科
背景:
- IgA腎不全 (IgAN) は,粘膜の免疫機能障害と腎臓のIgA蓄積を伴うもので,患者の20~40%で腎機能低下と末期腎疾患を引き起こします.
- 現在,IgANの治療は限られており,疾患の根本的なメカニズムを標的とした新しい治療戦略の必要性を強調しています.
研究 の 目的:
- IgA腎不全の患者において,新しい標的放出薬剤であるブデソニド (TRF-ブデソニド) の安全性と有効性を評価する.
- タンパク質尿を減らし,病気の進行を遅らせる能力を評価する.
主な方法:
- バイオプシーで確認されたIgANと,最適化されたレニン- 血管新生系 (RAS) 阻害にもかかわらず持続するタンパク質ウリアの患者150人を対象としたランダム化,ダブルブラインド,プラセボ対照フェーズ2b試験 (NEFIGAN).
- 患者は9ヶ月間,TRF- ブデソニド16 mg/ 日,TRF- ブデソニド8 mg/ 日,またはプラセボを投与され,主なアウトカムはタンパク質尿 (尿中のタンパク質クレアチニン比率 - UPCR) でした.
- 副作用のモニタリングを含む安全性評価が行われました.
主要な成果:
- TRF-ブデソニド投与 (16 mg/日および8 mg/日併用) は,プラセボと比較して9ヶ月でUPCRの有意な平均減少をもたらしました (p=0. 0066).
- 16 mg/ 日 (27. 3%) と8 mg/ 日 (21. 5%) の投与量では,プラセボと比較してUPCRが有意に低下した.
- 2つの重篤な有害事象は,TRF-ブデソニドと関連している可能性がある.
結論:
- TRF- ブデソニドは,最適化されたRAS阻害に添加されると,IgA腎不全患者のタンパク質尿を効果的に減少させます.
- タンパク質尿の減少は,末期性腎疾患への進行リスクの潜在的減少を示唆する.
- TRF- ブデソニドは,腎臓発現の前流の腸内粘膜免疫を標的とした最初の特定の治療法である可能性があります.
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