PMID- 24289915 OWN - NLM STAT- MEDLINE DCOM- 20140327 LR - 20220409 IS - 1549-4713 (Electronic) IS - 0161-6420 (Linking) VI - 121 IP - 2 DP - 2014 Feb TI - Lifitegrast ophthalmic solution 5.0% for treatment of dry eye disease: results of the OPUS-1 phase 3 study. PG - 475-83 LID - S0161-6420(13)00835-X [pii] LID - 10.1016/j.ophtha.2013.09.015 [doi] AB - PURPOSE: To assess the efficacy and safety of lifitegrast ophthalmic solution 5.0% compared with placebo in subjects with dry eye disease. DESIGN: Prospective, randomized, double-masked, placebo-controlled, parallel arm, multicenter clinical trial. PARTICIPANTS: A total of 588 adult subjects with dry eye disease. METHODS: Eligible subjects were randomized 1:1 to receive topically administered lifitegrast (5.0%) or placebo (vehicle) twice daily for 84 days after a 14-day open-label placebo run-in period. After enrollment (day 0), subjects were evaluated at days 14, 42, and 84. Key objective (fluorescein and lissamine staining scores [Ora scales]) and subjective (Ocular Surface Disease Index [OSDI], 7-item visual analog scale, and ocular discomfort score [Ora scale]) measures were assessed at all visits. MAIN OUTCOME MEASURES: The primary objective efficacy measure (sign) was mean change from baseline inferior corneal staining score (ICSS) at day 84. The co-primary subjective efficacy measure (symptom) was the mean change from baseline in the visual-related function subscale score of the Ocular Surface Disease Index (VR-OSDI). Supportive measures included corneal fluorescein scores (superior, central, total region) and conjunctival lissamine scores (nasal, temporal, total region) and symptom scores at day 84. RESULTS: The study met the primary objective efficacy ICSS end point in demonstrating superiority of lifitegrast compared with placebo (P = 0.0007). Lifitegrast significantly reduced corneal fluorescein staining (superior, P = 0.0392; total cornea, P = 0.0148) and conjunctival lissamine staining (nasal, P = 0.0039; total conjunctiva, P = 0.0086) at day 84 versus placebo. Significant (P < 0.05) improvements in nasal and total lissamine scores were observed at day 14 and maintained through day 84. The study did not meet the co-primary subjective VR-OSDI measure (P = 0.7894). However, significant improvements were observed at day 84 in ocular discomfort (P = 0.0273) and eye dryness (P = 0.0291), the most common and severe symptoms reported at baseline in both groups. There were no unanticipated or serious ocular adverse events (AEs). The most frequent reported ocular AEs were transient intermittent instillation site symptoms (irritation, discomfort) primarily on the initial lifitegrast dose at day 0. CONCLUSIONS: Lifitegrast ophthalmic solution 5.0% significantly reduced corneal fluorescein and conjunctival lissamine staining and improved symptoms of ocular discomfort and eye dryness compared with placebo when administered twice daily over 84 days. CI - Copyright (c) 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved. FAU - Sheppard, John D AU - Sheppard JD AD - Virginia Eye Consultants and Eastern Virginia Medical School, Norfolk, Virginia. FAU - Torkildsen, Gail L AU - Torkildsen GL AD - Andover Eye Associates, Andover, Massachusetts. FAU - Lonsdale, John D AU - Lonsdale JD AD - Central Maine Eye Care, Lewiston, Maine. FAU - D'Ambrosio, Francis A Jr AU - D'Ambrosio FA Jr AD - D'Ambrosio Eye Care, Lancaster, Massachusetts. FAU - McLaurin, Eugene B AU - McLaurin EB AD - Total Eye Care, Memphis, Tennessee. FAU - Eiferman, Richard A AU - Eiferman RA AD - University of Louisville, Louisville, Kentucky. FAU - Kennedy, Kathryn S AU - Kennedy KS AD - Independent Biostatistical Consultants, Tempe, Arizona. FAU - Semba, Charles P AU - Semba CP AD - SARcode Bioscience, Inc, Brisbane, California. Electronic address: csemba@shire.com. CN - OPUS-1 Study Group LA - eng PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20131126 PL - United States TA - Ophthalmology JT - Ophthalmology JID - 7802443 RN - 0 (Lissamine Green Dyes) RN - 0 (Lymphocyte Function-Associated Antigen-1) RN - 0 (Ophthalmic Solutions) RN - 0 (Sulfones) RN - 038E5L962W (lifitegrast) RN - 47E5O17Y3R (Phenylalanine) RN - TPY09G7XIR (Fluorescein) SB - IM MH - Administration, Topical MH - Adult MH - Aged MH - Aged, 80 and over MH - Conjunctiva/metabolism MH - Cornea/metabolism MH - Double-Blind Method MH - Dry Eye Syndromes/*drug therapy/metabolism/physiopathology MH - Female MH - Fluorescein/metabolism MH - Fluorometry MH - Humans MH - Lissamine Green Dyes/metabolism MH - Lymphocyte Function-Associated Antigen-1/*drug effects MH - Male MH - Middle Aged MH - Ophthalmic Solutions MH - Phenylalanine/administration & dosage/adverse effects/*analogs & derivatives MH - Prospective Studies MH - Staining and Labeling MH - Sulfones/*administration & dosage/adverse effects MH - Treatment Outcome MH - Young Adult FIR - Correnti, Anthony J IR - Correnti AJ FIR - D'Ambrosio, Francis A IR - D'Ambrosio FA FIR - Eiferman, Richard A IR - Eiferman RA FIR - Evans, Douglas IR - Evans D FIR - Geffin, Joel A IR - Geffin JA FIR - Greiner, Jack V IR - Greiner JV FIR - Lonsdale, John D IR - Lonsdale JD FIR - McLaurin, Eugene B IR - McLaurin EB FIR - Nielsen, Steven A IR - Nielsen SA FIR - Torkildsen, Gail L IR - Torkildsen GL FIR - Schumacher-Feero, Linda A IR - Schumacher-Feero LA FIR - Sheppard, John D IR - Sheppard JD FIR - Spindel, Gerald P IR - Spindel GP EDAT- 2013/12/03 06:00 MHDA- 2014/03/29 06:00 CRDT- 2013/12/03 06:00 PHST- 2013/04/06 00:00 [received] PHST- 2013/08/14 00:00 [revised] PHST- 2013/09/12 00:00 [accepted] PHST- 2013/12/03 06:00 [entrez] PHST- 2013/12/03 06:00 [pubmed] PHST- 2014/03/29 06:00 [medline] AID - S0161-6420(13)00835-X [pii] AID - 10.1016/j.ophtha.2013.09.015 [doi] PST - ppublish SO - Ophthalmology. 2014 Feb;121(2):475-83. doi: 10.1016/j.ophtha.2013.09.015. Epub 2013 Nov 26.