Lifitegrast Ophthalmic Solution 5.0% versus Placebo for Treatment of Dry Eye Disease

Tauber, Joseph; Karpecki, Paul; Latkany, Robert; Luchs, Jodi; Martel, James B.; Sall, Kenneth; Raychaudhuri, Aparna; Smith, Valerie; Semba, Charles P.

doi:10.1016/j.ophtha.2015.08.001

Cited by 147 publications

(183 citation statements)

References 16 publications

(15 reference statements)

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“…Full methodology for each of the studies discussed in this article can be found in the primary study publications [9][10][11] . Table 1 gives an overview of the three studies.…”

Section: Methodsmentioning

confidence: 99%

“…The results of three randomized controlled trials investigating the clinical efficacy and safety of lifitegrast ophthalmic solution for the treatment of DED have been reported to date (one phase 2 and two phase 3 trials [OPUS-1 and OPUS-2]) [9][10][11] . These three multicenter, randomized, placebo-controlled trials were carried out in the US over a period of 4 years between 2009 and 2013, and involved over 1500 participants.…”

Section: Introductionmentioning

confidence: 99%

“…The first phase 3 trial, OPUS-1 10 , evaluated the effect of lifitegrast ophthalmic solution 5.0% on signs and symptoms of DED in a larger population of participants with mild-to-moderate baseline DED symptomatology. OPUS-2 11 , a subsequent phase 3 trial, investigated the effect of lifitegrast ophthalmic solution 5.0% in participants with moderate-to-severe DED symptomatology. A third phase 3 trial, OPUS-3, was also recently completed in patients with moderate-to-severe symptomatology; results of this trial will be reported in a future publication.…”

Section: Introductionmentioning

confidence: 99%

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Lifitegrast clinical efficacy for treatment of signs and symptoms of dry eye disease across three randomized controlled trials

Holland

Whitley

Sall

et al. 2016

Current Medical Research and Opinion

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Objective: Report efficacy findings from three clinical trials (one phase 2 and two phase 3 [OPUS-1, OPUS-2]) of lifitegrast ophthalmic solution 5.0% for treatment of dry eye disease (DED). Research design and methods: Three 84-day, randomized, double-masked, placebo-controlled trials. Adults (!18 years) with DED were randomized (1:1) to lifitegrast 5.0% or matching placebo. Changes from baseline to day 84 in signs and symptoms of DED were analyzed. Main outcome measures: Phase 2, pre-specified endpoint: inferior corneal staining score (ICSS; 0-4); OPUS-1, coprimary endpoints: ICSS and visual-related function subscale (0-4 scale); OPUS-2, coprimary endpoints: ICSS and eye dryness score (EDS, VAS; 0-100). Results: Fifty-eight participants were randomized to lifitegrast 5.0% and 58 to placebo in the phase 2 trial; 293 to lifitegrast and 295 to placebo in OPUS-1; 358 to lifitegrast and 360 to placebo in OPUS-2. In participants with mild-to-moderate baseline DED symptomatology, lifitegrast improved ICSS versus placebo in the phase 2 study (treatment effect, 0.35; 95% CI, 0.05-0.65; p ¼ 0.0209) and OPUS-1 (effect, 0.24; 95% CI, 0.10-0.38; p ¼ 0.0007). Among more symptomatic participants (baseline EDS !40, recent artificial tear use), lifitegrast improved EDS versus placebo in a post hoc analysis of OPUS-1 (effect, 13.34; 95% CI, 2.35-24.33; nominal p ¼ 0.0178) and in OPUS-2 (effect, 12.61; 95% CI, 8.51-16.70; p < 0.0001). Limitations: Trials were conducted over 12 weeks; efficacy beyond this period was not assessed. Conclusions: Across three trials, lifitegrast improved ICSS in participants with mild-to-moderate baseline symptomatology in two studies, and EDS in participants with moderate-to-severe baseline symptomatology in two studies. Based on the overall findings from these trials, lifitegrast shows promise as a new treatment option for signs and symptoms of DED. ARTICLE HISTORY

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“…Full methodology for each of the studies discussed in this article can be found in the primary study publications [9][10][11] . Table 1 gives an overview of the three studies.…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Lifitegrast clinical efficacy for treatment of signs and symptoms of dry eye disease across three randomized controlled trials

Holland

Whitley

Sall

et al. 2016

Current Medical Research and Opinion

Self Cite

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show abstract

“…The clinical efficacy and safety of lifitegrast in DED have been demonstrated across 5 randomized controlled trials, including 1 phase 2 trial 63 and 4 phase 3 trials: OPUS-1, 64 OPUS-2, 65 OPUS-3 (NCT02284516; publication in development), and the long-term, randomized, double-masked safety study SONATA. 66 In the Phase 2 and OPUS-1 trials, lifitegrast showed significant improvement from baseline to day 84 versus placebo in the sign endpoint of inferior corneal staining score (Phase 2: secondary endpoint, nominal P = 0.0209; OPUS-1: coprimary endpoint, P = 0.0007).…”

Section: Targeting Lfa-1/icam-1 Interaction In Dedmentioning

confidence: 99%

LFA-1/ICAM-1 Interaction as a Therapeutic Target in Dry Eye Disease

Pflugfelder

Stern

Zhang

et al. 2017

Journal of Ocular Pharmacology and Therapeutics

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Dry eye disease (DED) is a common ocular disorder associated with inflammation of the lacrimal gland and ocular surface. The interaction of the integrin lymphocyte function-associated antigen-1 (LFA-1) with its cognate ligand intercellular adhesion molecule-1 (ICAM-1) is known to have important roles in the interaction of a variety of cells involved in immune responses and inflammation, including those prominent in ocular surface inflammation. Lifitegrast, an LFA-1 antagonist that blocks binding of ICAM-1 to LFA-1, has recently been approved in the United States for the treatment of signs and symptoms of DED. In this review, we evaluate research findings to explore the potential role of LFA-1/ICAM-1 interaction in the pathophysiology of DED, and the evidence supporting LFA-1/ICAM-1 interaction as a rational therapeutic target in DED. The results of our review suggest that LFA-1/ICAM-1 interaction may play important roles in the cell-mediated immune response and inflammation associated with DED, including facilitating the homing of dendritic cells to the lymph nodes, interaction of dendritic cells with T cells and subsequent T cell activation/differentiation, migration of activated CD4+ T cells from the lymph nodes to the ocular surface, reactivation of T cells by resident antigen-presenting cells at the ocular surface, and recruitment and retention of LFA-1-expressing T cells in the conjunctival epithelium. Based on the available evidence, inhibition of LFA-1/ICAM-1 interaction represents a rational targeted approach in treating DED. Notably, inhibition of LFA-1/ICAM-1 binding with lifitegrast offers a novel approach to reducing ocular surface inflammation in this condition.

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“…At 12 weeks, primary endpoints included change from baseline to 12 weeks, from baseline in eye dryness as measured on the visual analog scale as well as ocular signs of keratoconjunctivitis sicca (inferior corneal fluorescein staining in the study eye). While there was a statistically significant greater improvement in patientreported symptoms in eye dryness in the lifitegrast group compared to placebo, there was no difference between the two arms with respect to inferior corneal staining with fluorescein [26].…”

Section: Lifitegrastmentioning

confidence: 75%