TY - JOUR
T1 - A pilot 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
AU - Kheirkhah, Ahmad
AU - Di Zazzo, Antonio
AU - Satitpitakul, Vannarut
AU - Fernandez, Merle
AU - Magilavy, Daniel
AU - Dana, Reza
N1 - Publisher Copyright:
© 2017 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2017
Y1 - 2017
N2 - Purpose: Janus kinase (JAK) and spleen tyrosine kinase (SYK) play critical functions in T-cell activation and in inflammation. Because of their antiinflammatory effects, JAK and SYK inhibitors have recently been evaluated in several immunopathogenic disorders. This pilot study was designed to assess the safety and efficacy of a topical combined JAK/SYK inhibitor, R348, ophthalmic solution for treatment of ocular surface disease in graft-versus-host disease (GVHD). Methods: This phase 2, double-masked, randomized, pilot trial included 30 patients with ocular surface disease due to GVHD who were randomized to receive 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 questionnaire, corneal fluorescein staining, conjunctival lissamine green staining, and Schirmer test with anesthesia. Changes in these parameters were compared between the 3 groups. Results: The mean decrease in total corneal fluorescein staining at 12 weeks after treatment was higher in the 0.5% R348 group (26.0 ± 3.9, NEI scoring) compared with the vehicle (22.1 ± 2.6, P = 0.045) or the 0.2% R348 group (24.1 ± 3.6, P = 0.34). However, there were no significant differences among the groups in terms of treatment-induced changes in OSDI, Ocular Comfort Index, conjunctival lissamine green staining, or Schirmer scores. R348 eye drops were well tolerated. Conclusions: This pilot study indicates that 0.5% R348 JAK/SYK inhibitor ophthalmic solution is well tolerated and may have some therapeutic efficacy in treating ocular GVHD. Larger trials are required to derive more definitive data.
AB - Purpose: Janus kinase (JAK) and spleen tyrosine kinase (SYK) play critical functions in T-cell activation and in inflammation. Because of their antiinflammatory effects, JAK and SYK inhibitors have recently been evaluated in several immunopathogenic disorders. This pilot study was designed to assess the safety and efficacy of a topical combined JAK/SYK inhibitor, R348, ophthalmic solution for treatment of ocular surface disease in graft-versus-host disease (GVHD). Methods: This phase 2, double-masked, randomized, pilot trial included 30 patients with ocular surface disease due to GVHD who were randomized to receive 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 questionnaire, corneal fluorescein staining, conjunctival lissamine green staining, and Schirmer test with anesthesia. Changes in these parameters were compared between the 3 groups. Results: The mean decrease in total corneal fluorescein staining at 12 weeks after treatment was higher in the 0.5% R348 group (26.0 ± 3.9, NEI scoring) compared with the vehicle (22.1 ± 2.6, P = 0.045) or the 0.2% R348 group (24.1 ± 3.6, P = 0.34). However, there were no significant differences among the groups in terms of treatment-induced changes in OSDI, Ocular Comfort Index, conjunctival lissamine green staining, or Schirmer scores. R348 eye drops were well tolerated. Conclusions: This pilot study indicates that 0.5% R348 JAK/SYK inhibitor ophthalmic solution is well tolerated and may have some therapeutic efficacy in treating ocular GVHD. Larger trials are required to derive more definitive data.
KW - Dry eye disease
KW - GVHD
KW - Janus kinase
KW - Ocular surface disease
KW - Spleen tyrosine kinase
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U2 - 10.1097/ICO.0000000000001206
DO - 10.1097/ICO.0000000000001206
M3 - Article
C2 - 28445193
AN - SCOPUS:85020919651
SN - 0277-3740
VL - 36
SP - 799
EP - 804
JO - Cornea
JF - Cornea
IS - 7
ER -