低用量ブリモニジンによる眼精疲労の緩和：4つの臨床試験の統合的解析

Low-dose brimonidine for relief of ocular redness: integrated analysis of four clinical trials.

• Stacey L Ackerman
• Gail L Torkildsen
• Eugene McLaurin
• Jason L Vittitow

抄録

背景:

BACKGROUND: The aim of this study was to provide an integrated analysis of safety and efficacy data for brimonidine tartrate ophthalmic solution 0.025 per cent (low-dose; Bausch & Lomb Incorporated), a topical vasoconstrictor for relief of ocular redness.

方法:

眼部充血を対象とした2つの無作為化、ダブルマスク、薬物動態試験の統合的な有効性データと、2つの有効性試験、薬物動態試験、薬物動態試験の安全性データを解析しました。有効性のアウトカムは、投与前、投与1日目の5～240分後、投与15日目と29日目の5分後、投与中止1週間後（36日目）の眼球発赤度（0～4段階）、被験者が毎日日記に記録した眼球発赤度の自己評価、および安全性の評価は、有害事象、眼球発赤度、薬物動態試験、薬物動態試験のデータを解析しました。安全性評価には、有害事象、眼科検査、治療中止時の赤みの反動が含まれた。落ちつきやすさ（0～10の尺度）を忍容性の指標とした。

METHODS: Integrated efficacy data from two randomised, double-masked, vehicle-controlled studies in subjects with ocular redness as well as safety data from the two efficacy studies, a vehicle-controlled safety study, and a pharmacokinetic study were analysed. Efficacy outcomes analysed included investigator-assessed ocular redness (scale, 0-4) before treatment instillation and at five to 240 minutes post-instillation on Day 1, at five minutes post-instillation on Days 15 and 29, and one week after treatment discontinuation (Day 36), and redness self-assessed by subjects recorded daily in diaries. Safety assessments included adverse events, ophthalmic examinations, and rebound redness upon treatment discontinuation. Drop comfort (scale, 0-10) was a tolerability measure.

結果:

有効性集団は117名（ブリモニジン、n=78、ビヒクル、n=39）であった。安全性集団には635例が含まれた（ブリモニジン、n=426；ビヒクル、n=209）。被験者の眼球発赤度評価は、ブリモニジン投与1日目のすべての投与後時間帯において、ブリモニジン投与群とビヒクル投与群で有意に低かった（ブリモニジン投与前からの平均変化量はブリモニジン-1.4単位、ビヒクル投与群-0.2単位、p<0.0001）。また、被験者が評価した眼の赤みもブリモニジンとビヒクルで有意に低かった（1日平均評価の平均治療差-0.9；p<0.0001）。29日目までタキフィラキシーは認められず、リバウンド赤みはまれでした。眼の有害事象の発現率は低く、最も多かったのは視力低下（ブリモニジン：4.0％、ビヒクル：4.3％）と結膜充血（それぞれ2.6％、2.9％）でした。また，ブリモニジン，ビヒクルともに非常に快適であると評価された（注入後の平均スコア，0.4～0.5）．

RESULTS: The efficacy population included 117 subjects (brimonidine, n = 78; vehicle, n = 39). The safety population included 635 subjects (brimonidine, n = 426; vehicle, n = 209). Investigator-assessed ocular redness was significantly lower with brimonidine versus vehicle at all post-instillation time points on Day 1 (mean change from pre-instillation of -1.4 units for brimonidine and -0.2 units for vehicle; p < 0.0001). Subject-assessed ocular redness was also significantly lower with brimonidine versus vehicle (mean treatment difference in average daily ratings of -0.9; p < 0.0001). There was no evidence of tachyphylaxis through Day 29 and rebound redness was rare. Incidence of ocular adverse events was low, the most common being reduced visual acuity (brimonidine, 4.0 per cent; vehicle, 4.3 per cent) and conjunctival hyperaemia (2.6 and 2.9 per cent, respectively). Both brimonidine and vehicle were rated as very comfortable (mean post-instillation scores, 0.4-0.5).

結論:

この統合解析では、低用量ブリモニジンはタキフィラキシーを伴わない眼球赤みを有意に減少させ、リバウンド赤みを最小限に抑え、全般的に安全性と忍容性に優れていました。

CONCLUSION: In this integrated analysis, low-dose brimonidine significantly reduced ocular redness with no tachyphylaxis, and minimal rebound redness, and was generally safe and well tolerated.

© 2018 The Authors. Clinical and Experimental Optometry published by John Wiley & Sons Australia, Ltd on behalf of Optometry Australia.