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Ahmad Kheirkhah, Antonio Di Zazzo, Vannarut Satitpitakul, Merle Fernandez, Daniel Magilavy, Reza Dana; A Randomized Trial on Safety and Efficacy of a Novel Topical Combined Inhibitor of Janus Kinase 1/3 and Spleen Tyrosine Kinase for GVHD-associated Ocular Surface Disease. Invest. Ophthalmol. Vis. Sci. 2017;58(8):3752. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Janus Kinase (JAK) and Spleen Tyrosine Kinase (SYK) play critical functions in T cell activation and in inflammation. Due to their anti-inflammatory effects, JAK and SYK inhibitors have recently been evaluated in several immunopathogenic disorders. This study was designed to assess the safety and efficacy of a topical combined JAK 1/3 and SYK inhibitor (R348) ophthalmic solution for treatment of ocular surface disease in ocular graft-versus-host disease (GVHD).
This Phase 2, double-masked, randomized trial included 30 patients with ocular surface disease due to GVHD who were randomized to receive either topical 0.5% R348, 0.2% R348, or vehicle, twice daily for 12 weeks. Before and after treatment, a comprehensive ophthalmic evaluation was performed which included Ocular Surface Disease Index (OSDI) questionnaire, Ocular Comfort Index (OCI) questionnaire, corneal fluorescein staining, conjunctival lissamine green staining, and Schirmer test with anesthesia. Changes in these parameters were compared between the three groups.
The mean decrease in total corneal fluorescein staining at 12 weeks after treatment was higher in the 0.5% R348 group (-6.0±3.9, NEI scoring) compared with vehicle (-2.1±2.6, P=0.045) or the 0.2% R348 group (-4.1±3.6, P=0.34). However, there were no significant differences between the groups in terms of treatment-induced changes in OSDI, OCI, conjunctival lissamine green staining, or Schirmer scores. R348 eye drops were well tolerated.
This Phase 2, randomized trial indicates that 0.5% R348 JAK/SYK inhibitor ophthalmic solution is well tolerated and has some therapeutic efficacy in treating ocular GVHD. Larger trials are required to derive more definitive data.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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