Safety of Lifitegrast Ophthalmic Solution 5.0% in Patients With Dry Eye Disease

Donnenfeld, Eric D.; Karpecki, Paul; Majmudar, Parag A.; Nichols, Kelly K.; Raychaudhuri, Aparna; Roy, Monica; Semba, Charles P.

doi:10.1097/ico.0000000000000803

Cited by 82 publications

(99 citation statements)

References 15 publications

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“…SONATA demonstrated that the long-term safety profile of lifitegrast ophthalmic solution 5.0% was similar to the 12 week studies, with no unexpected adverse events over a prolonged period of use 13 . Based on the overall findings from these clinical studies, lifitegrast has shown promise as a new treatment option for signs and symptoms of DED.…”

Section: General Discussion and Conclusionmentioning

confidence: 94%

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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Section: General Discussion and Conclusionmentioning

confidence: 94%

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

View full text Add to dashboard Cite

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“…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). In the OPUS-2 and OPUS-3 trials, lifitegrast-treated participants experienced significantly greater improvement from baseline to day 84 in the symptom endpoint of eye dryness score (visual analogue scale) versus placebo (OPUS-2: coprimary endpoint, P < 0.0001; OPUS-3: primary endpoint, P = 0.0007).…”

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

confidence: 98%

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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“…Systemic administration of antibodies against intercellular adhesion molecule (ICAM)-1, leukocyte function antigen (LFA)-1, very late antigen (VLA)-1 and VLA-4 in mice has resulted in inhibition of graft rejection [74–76]. It will be interesting to see if an upcoming new topical therapy for dry eyes, (Lifitegrast), which similarly inhibits adhesion molecules [77], will have any effect on graft rejection.…”

Section: Experimental Approachesmentioning

confidence: 99%

Update on the Management of High-Risk Penetrating Keratoplasty

Jabbehdari

Rafii

Yazdanpanah

et al. 2017

Curr Ophthalmol Rep

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Purpose of review In this article, we review the indications and latest management of high-risk penetrating keratoplasty. Recent findings Despite the immune-privilege status of the cornea, immune-mediated graft rejection still remains the leading cause of corneal graft failure. This is particularly a problem in the high-risk graft recipients, namely patients with previous graft failure due to rejection and those with inflamed and vascularized corneal beds. A number of strategies including both local and systemic immunosuppression are currently used to increase the success rate of high-risk corneal grafts. Moreover, in cases of limbal stem cell deficiency, limbal stem cells transplantation is employed. Summary Corticosteroids are still the top medication for prevention and treatment in cases of corneal graft rejection. Single and combined administration of immunosuppressive agents e.g. tacrolimus, cyclosporine and mycophenolate are promising adjunctive therapies for prolonging graft survival. In the future, cellular and molecular therapies should allow us to achieve immunologic tolerance even in high-risk grafts.

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Safety of Lifitegrast Ophthalmic Solution 5.0% in Patients With Dry Eye Disease

Abstract: Supplemental Digital Content is Available in the Text.

Cited by 82 publications

References 15 publications

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

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

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

Update on the Management of High-Risk Penetrating Keratoplasty

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