Skip to main content
SpringerLink
Log in

Lifitegrast Ophthalmic Solution 5%: A Review in Dry Eye Disease

  • Adis Drug Evaluation
  • Published:
Drugs Aims and scope Submit manuscript

Abstract

Lifitegrast is a novel small molecule integrin antagonist that blocks the binding of intercellular adhesion molecule 1 (ICAM-1) to lymphocyte function-associated antigen 1 (LFA-1). Lifitegrast ophthalmic solution 5% (Xiidra™) was recently approved in the USA for the treatment of dry eye disease. The efficacy of lifitegrast ophthalmic solution 5% was compared with vehicle in a 12-week phase 2 study and three 12-week phase 3 studies (OPUS-1, OPUS-2 and OPUS-3) in patients with dry eye disease. Taken as a whole, results of these trials support the treatment effect of lifitegrast ophthalmic solution 5% in improving a symptom of dry eye disease (i.e. the change from baseline to day 84 in the eye dryness visual analogue scale score) and a sign of dry eye disease (i.e. the change from baseline to day 84 in the inferior corneal fluorescein staining score). Lifitegrast ophthalmic solution 5% was generally well tolerated. In conclusion, lifitegrast ophthalmic solution 5% provides a new option for the treatment of dry eye disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. The definition and classification of dry eye disease: report of the Definition and Classification Subcommittee of the International Dry Eye WorkShop (2007). Ocul Surf. 2007;5(2):75–92.

  2. Semba CP, Gadek TR. Development of lifitegrast: a novel T-cell inhibitor for the treatment of dry eye disease. Clin Ophthalmol. 2016;10:1083–94.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Gao J, Morgan G, Tieu D, et al. ICAM-1 expression predisposes ocular tissues to immune-based inflammation in dry eye patients and Sjögrens syndrome-like MRL/lpr mice. Exp Eye Res. 2004;78(4):823–35.

    Article  CAS  PubMed  Google Scholar 

  4. Stern ME, Gao J, Schwalb TA, et al. Conjunctival T-cell subpopulations in Sjögren’s and non-Sjögren’s patients with dry eye. Invest Ophthalmol Vis Sci. 2002;43(8):2609–14.

    PubMed  Google Scholar 

  5. Perez VL, Pflugfelder SC, Zhang S, et al. Lifitegrast, a novel integrin antagonist for treatment of dry eye disease. Ocul Surf. 2016;14(2):207–15.

    Article  PubMed  Google Scholar 

  6. Allergan Inc. Restasis® (cyclosporine ophthlamic emulsion) 0.05%: US prescribing information. 2013. http://www.allergan.com/assets/pdf/restasis_pi.pdf. Accessed 7 Dec 2016.

  7. Shire US Inc. Xiidra™ (lifitegrast ophthalmic solution) 5% for topical ophthalmic use: US prescribing information. 2016. http://www.shirecontent.com/PI/PDFs/Xiidra_USA_ENG.pdf. Accessed 7 Dec 2016.

  8. Zhong M, Gadek TR, Bui M, et al. Discovery and development of potent LFA-1/ICAM-1 antagonist SAR 1118 as an ophthalmic solution for treating dry eye. ACS Med Chem Lett. 2012;3(3):203–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Murphy CJ, Bentley E, Miller PE, et al. The pharmacologic assessment of a novel lymphocyte function-associated antigen-1 antagonist (SAR 1118) for the treatment of keratoconjunctivitis sicca in dogs. Invest Ophthalmol Vis Sci. 2011;52(6):3174–80.

    Article  CAS  PubMed  Google Scholar 

  10. Lam H, Bleiden L, de Paiva CS, et al. Tear cytokine profiles in dysfunctional tear syndrome. Am J Ophthalmol. 2009;147(2):198–205.

    Article  CAS  PubMed  Google Scholar 

  11. Sun Y, Zhang R, Gadek TR, et al. Corneal inflammation is inhibited by the LFA-1 antagonist, lifitegrast (SAR 1118). J Ocul Pharmacol Ther. 2013;29(4):395–402.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Semba CP, Swearingen D, Smith VL, et al. Safety and pharmacokinetics of a novel lymphocyte function-associated antigen-1 (LFA-1) antagonist ophthalmic solution (SAR 1118) in healthy adults. J Ocul Pharmacol Ther. 2011;27(1):99–104.

    Article  CAS  PubMed  Google Scholar 

  13. Donnenfeld ED, Karpecki PM, Majmudar PA, et al. Safety of lifitegrast ophthalmic solution 5.0% in patients with dry eye disease: a 1-year, multicenter, randomized, placebo-controlled study. Cornea. 2016;35(6):741–8.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Rao VR, Prescott E, Shelke NB, et al. Delivery of SAR 1118 to the retina via ophthalmic drops and its effectiveness in a rat streptozotocin (STZ) model of diabetic retinopathy (DR). Invest Ophthalmol Vis Sci. 2010;51(10):5198–204.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Semba CP, Torkildsen GL, Lonsdale JD, et al. A phase 2 randomized, double-masked, placebo-controlled study of a novel integrin antagonist (SAR 1118) for the treatment of dry eye. Am J Ophthalmol. 2012;153(6):1050–60.

    Article  CAS  PubMed  Google Scholar 

  16. Sheppard JD, Torkildsen GL, Lonsdale JD, et al. Lifitegrast ophthalmic solution 5.0% for treatment of dry eye disease: results of the OPUS-1 phase 3 study. Ophthalmology. 2014;121(2):475–83.

    Article  PubMed  Google Scholar 

  17. Tauber J, Karpecki P, Latkany R, et al. Lifitegrast ophthalmic solution 5.0% versus placebo for treatment of dry eye disease: results of the randomized phase III OPUS-2 study. Ophthalmology. 2015;122(12):2423–31.

    Article  PubMed  Google Scholar 

  18. Holland EJ, Luchs J, Karpecki PM, et al. Lifitegrast for the treatment of dry eye disease: results of a phase III, randomized, double-masked, placebo-controlled trial (OPUS-3). Ophthalmology. 2016. doi:10.1016/j.ophtha.2016.09.025.

    Google Scholar 

  19. Holland EJ, Whitley WO, Sall K, et al. Lifitegrast clinical efficacy for treatment of signs and symptoms of dry eye disease across three randomized controlled trials. Curr Med Res Opin. 2016. doi:10.1080/03007995.2016.1210107.

    PubMed  Google Scholar 

  20. Management and therapy of dry eye disease: report of the Management and Therapy Subcommittee of the International Dry Eye WorkShop (2007). Ocul Surf. 2007;5(2):163–78.

  21. Food and Drug Administration. Application number 208073Orig1s000: summary review. 2016. http://www.fda.gov. Accessed 7 Dec 2016.

  22. Nichols KK, Nichols JJ, Mitchell GL. The lack of association between signs and symptoms in patients with dry eye disease. Cornea. 2004;23(8):762–70.

    Article  PubMed  Google Scholar 

  23. Bartlett JD, Keith MS, Sudharshan L, et al. Associations between signs and symptoms of dry eye disease: a systematic review. Clin Ophthalmol. 2015;9:1719–30.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

During the peer review process, the manufacturer of lifitegrast ophthalmic solution 5% was also offered an opportunity to review this article. Changes resulting from comments received were made on the basis of scientific and editorial merit.

Author information

Authors and Affiliations

  1. Springer, Private Bag 65901, Mairangi Bay, 0754, Auckland, New Zealand

    Gillian M. Keating

Authors
  1. Gillian M. Keating
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gillian M. Keating.

Ethics declarations

Funding

The preparation of this review was not supported by any external funding.

Conflict of interest

Gillian Keating is a salaried employee of Adis/Springer, is responsible for the article content and declares no relevant conflicts of interest.

Additional information

The manuscript was reviewed by: M. A. Lemp, Department of Ophthalmology, Georgetown University, Washington, DC, USA; S. C. Pflugfelder, Ocular Surface Center, Department of Ophthalmology, Baylor College of Medicine, Houston, TX, USA.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Keating, G.M. Lifitegrast Ophthalmic Solution 5%: A Review in Dry Eye Disease. Drugs 77, 201–208 (2017). https://doi.org/10.1007/s40265-016-0681-1

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40265-016-0681-1

Keywords

Search

Navigation