sar-1118 and Keratoconjunctivitis-Sicca

Ocular chronic graft-versus-host disease (oGVHD) is a relatively common complication that occurs following allogeneic hematopoietic cell transplantation. Keratoconjunctivitis sicca (KCS) is the most common manifestation of oGVHD. Lifitegrast is a lymphocyte function-associated antigen-1 antagonist approved to reduce inflammation and symptoms in patients with dry eye disease. We evaluated the efficacy and safety of lifitegrast (5% ophthalmic solution) in patients with ocular GVHD in a single-institution retrospective cohort study of eighteen allogeneic transplant recipients who received topical lifitegrast for oGVHD treatment. The outcome of interest was improvement in oGVHD severity score by National Institutes of Health (NIH) criteria. Lifitegrast was well-tolerated and no serious adverse events were observed. Lifitegrast significantly improved NIH severity scores in 8 (44%) patients. The findings of this study suggest lifitegrast is safe, well-tolerated and is an effective option for oGVHD manifesting as KCS. Prospective evaluation is warranted to confirm efficacy of lifitegrast in this population.HighlightsIn this single-institution retrospective cohort study of eighteen patients who received allogeneic transplant between 2013 and 2018, and received topical lifitegrast for treatment of ocular GVHD, the results demonstrate that lifitegrast eye drops were well-tolerated and led to improvement in symptoms of KCS in 8 (44%) patients.Lifitegrast has the potential to fulfill an unmet need in allogeneic transplant patients with ocular GVHD. Further prospective study is warranted for confirmation.

Topics: Chronic Disease; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Keratoconjunctivitis Sicca; Phenylalanine; Prospective Studies; Retrospective Studies; Sulfones

Increased interferon gamma (IFN-γ) expression in dry eye causes ocular surface epithelial disease termed keratoconjunctivitis sicca (KCS). The purpose of this study was to investigated the effects of the LFA-1 antagonist, lifitegrast, in a mouse desiccating stress (DS) dry eye model that develops KCS similar to Sjögren syndrome.. Mice were treated with vehicle or lifitegrast twice daily for 5 days and expression of Th1 family genes (IFN-γ, CXCL9, and CXCL11) was evaluated by real-time polymerase chain reaction. Cornea barrier function was assessed by Oregon Green dextran staining and goblet cell number and area were measured.. Compared to the vehicle-treated group, the lifitegrast-treated group had significantly lower expression of Th1 family genes, less corneal barrier disruption, and greater conjunctival goblet cell density/area.. These findings indicate that lifitegrast inhibits DS-induced IFN-γ expression and KCS. This suggests that ICAM-LFA-1 signaling is involved with generation of Th1 inflammation in KCS.

Topics: Animals; Chemokine CXCL11; Chemokine CXCL9; Dry Eye Syndromes; Female; Inflammation; Interferon-gamma; Keratoconjunctivitis Sicca; Mice; Mice, Inbred C57BL; Ophthalmic Solutions; Phenylalanine; Sulfones; Th1 Cells

Topics: Administration, Ophthalmic; Humans; Keratoconjunctivitis Sicca; Ophthalmic Solutions; Phenylalanine; Randomized Controlled Trials as Topic; Sulfones