Tofacitinib (CP-690,550), a Janus kinase inhibitor for dry eye disease: results from a phase 1/2 trial

Ophthalmology. 2012 Jul;119(7):1328-35. doi: 10.1016/j.ophtha.2012.01.028. Epub 2012 Apr 22.


Objective: To evaluate safety and efficacy of topical ophthalmic tofacitinib (CP-690,550), a novel Janus kinase inhibitor, in treating dry eye disease (DED).

Design: A phase 1/2 prospective, randomized, double-masked, multicenter, vehicle- and comparator-controlled trial (NCT00784719).

Participants: Patients (n = 327) 18 years of age and older with a DED diagnosis for 6 months or more.

Methods: 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.

Main outcome measures: Schirmer wetting, corneal staining, tear film break-up time, conjunctival staining, Ocular Comfort Index (OCI), and Ocular Surface Disease Index (OSDI).

Results: 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<0.2, 2-sided) for all tofacitinib doses (1.7-3.1 mm), cyclosporine (3.9 mm), and vehicle (1.4 mm). For corneal staining (total score), significant improvement (reduction) from baseline was observed for all tofacitinib doses (-0.9 to -1.9) and vehicle (-2.0), but not for cyclosporine. The proportion of patients with complete corneal clearing (CCC; 100%) at week 8 was greatest with tofacitinib 0.005% once daily (15.9%) versus vehicle (6.7%). Symptom scores (OCI, OSDI) at week 8 showed significant improvements from baseline for all tofacitinib groups, and tofacitinib demonstrated greater improvements than cyclosporine. The tofacitinib 0.005% once daily group showed significant improvements in both a sign (Schirmer wetting without anesthesia) and symptom (OSDI environmental triggers subscale) versus vehicle and also demonstrated the highest response rate for CCC (16.7%) at week 8.

Conclusions: This phase 1/2 study of tofacitinib demonstrated a trend for improving both signs and symptoms of dry eye. All doses of tofacitinib exhibited a reasonable safety profile and were well tolerated by patients with DED.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cyclosporine / administration & dosage
  • Double-Blind Method
  • Dry Eye Syndromes / drug therapy*
  • Dry Eye Syndromes / metabolism
  • Dry Eye Syndromes / physiopathology
  • Female
  • Humans
  • Janus Kinase 3 / antagonists & inhibitors*
  • Male
  • Middle Aged
  • Ophthalmic Solutions
  • Piperidines
  • Prospective Studies
  • Pyrimidines / administration & dosage*
  • Pyrimidines / adverse effects
  • Pyrroles / administration & dosage*
  • Pyrroles / adverse effects
  • Surveys and Questionnaires
  • Tears / chemistry
  • Tears / physiology
  • Treatment Outcome


  • Ophthalmic Solutions
  • Piperidines
  • Pyrimidines
  • Pyrroles
  • Cyclosporine
  • tofacitinib
  • Janus Kinase 3

Associated data