Lifitegrast for the Treatment of Dry Eye Disease: Results of a Phase III, Randomized, Double-Masked, Placebo-Controlled Trial (OPUS-3)

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• 作者：Edward J. Holland ; MD¹ ; Jodi Luchs ; MD² ; Paul M. Karpecki ; OD ; FAAO³ ; Kelly K. Nichols ; OD ; PhD⁴ ; Mitchell A. Jackson ; MD⁵ ; Kenneth Sall ; MD⁶ ; Joseph Tauber ; MD⁷ ; Monica Roy ; OD ; MPH⁸ ; Aparna Raychaudhuri ; PhD⁸ ; Amir Shojaei ; PharmD ; PhD⁸ ; ^{ashojaei@shire.com}
• 关键词：AE ; adverse event ; CI ; confidence interval ; DCS ; drop comfort score ; DED ; dry eye disease ; EDS ; eye dryness score ; ICSS ; inferior corneal staining score ; ITT ; intention-to-treat ; ODS ; ocular discomfort score ; SD ; standard deviation ; TE ; treatment effect ; TEAE ; treatment-emergent adverse event ; VAS ; visual analogue scale
• 刊名：Ophthalmology
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：124
• 期：1
• 页码：53-60
• 全文大小：421 K
• 卷排序：124

文摘

Lifitegrast is a lymphocyte function–associated antigen-1 antagonist developed to reduce inflammation in dry eye disease (DED). We report the results of OPUS-3 (NCT02284516), a phase III study evaluating the efficacy and safety of lifitegrast versus placebo in participants with DED.DesignTwelve-week, phase III, randomized, double-masked, multicenter, placebo-controlled study.ParticipantsAdults aged ≥18 years with Schirmer tear test (without anesthesia) ≥1 and ≤10 mm, corneal fluorescein staining score ≥2.0 (0–4 scale), eye dryness score (EDS) ≥40 (0–100 visual analogue scale [VAS]), and history of artificial tear use within 30 days of study entry.MethodsAfter a 14-day placebo run-in, participants were randomized 1:1 to lifitegrast ophthalmic solution 5.0% or placebo twice daily for 84 days.Main Outcome MeasuresThe primary efficacy end point was change from baseline to day 84 in EDS. Key secondary efficacy end points were change from baseline to days 42 and 14 in EDS. Other secondary efficacy end points included additional VAS items (burning/stinging, itching, foreign body sensation, eye discomfort, photophobia, pain), ocular discomfort score (ODS), and safety/tolerability of lifitegrast versus placebo.ResultsIn the study, 711 participants were randomized: placebo, 356; lifitegrast, 355 (intention-to-treat [ITT] population). At day 84, lifitegrast-treated participants experienced significantly greater improvement from baseline in EDS versus those receiving placebo (treatment effect [TE], 7.16; 95% confidence interval [CI], 3.04–11.28; P = 0.0007). Mean changes from baseline in EDS also significantly favored lifitegrast on days 42 (TE, 9.32; 95% CI, 5.44–13.20; P < 0.0001) and 14 (TE, 7.85; 95% CI, 4.33–11.37; P < 0.0001). No statistically significant differences were observed in ODS between treatment groups at days 84, 42, or 14. A greater improvement was observed in lifitegrast-treated participants at day 42 in itching (nominal P = 0.0318), foreign body sensation (nominal P = 0.0418), and eye discomfort (P = 0.0048) versus participants receiving placebo. Most treatment-emergent adverse events were mild to moderate in severity; no serious ocular adverse events were reported.ConclusionsLifitegrast significantly improved symptoms of eye dryness, as measured by EDS, versus placebo in participants with DED. Improvement in EDS was observed as early as day 14. Lifitegrast appeared well tolerated.