Tofacitinib (CP-690,550), a Janus Kinase Inhibitor for Dry Eye Disease: Results from a Phase 1/2 Trial

To evaluate safety and efficacy of topical ophthalmic tofacitinib (CP-690,550), a novel Janus kinase inhibitor, in treating dry eye disease (DED). A phase 1/2 prospective, randomized, double-masked, multicenter, vehicle- and comparator-controlled trial (NCT00784719). Patients (n = 327) 18 years of age and older with a DED diagnosis for 6 months or more. Tofacitinib (0.0003% twice daily, n = 46; 0.001% in both eyes twice daily, n = 47; 0.003% twice daily, n = 48; 0.005% twice daily, n = 48; 0.005% once daily, n = 44) results were compared with those of groups receiving active treatment cyclosporine ophthalmic emulsion 0.05% twice daily (n = 47) and vehicle twice daily (n = 47). Safety and efficacy evaluations were performed at baseline and throughout the 8-week study. Schirmer wetting, corneal staining, tear film break-up time, conjunctival staining, Ocular Comfort Index (OCI), and Ocular Surface Disease Index (OSDI). All tofacitinib doses were well tolerated, exhibiting better patient-reported ocular tolerability than cyclosporine. For the proportion of patients achieving 10 mm or more Schirmer wetting (without anesthesia) at week 8 (primary end point), greater response rates were observed in the tofacitinib 0.001% twice daily (27.3%), 0.005% twice daily (25.5%), and 0.005% once daily (26.1%) groups versus vehicle (20.0%); however, the differences were not statistically significant. Mean increase in Schirmer wetting (without anesthesia) from baseline was statistically significant (P