title: Efficacy and safety of 0.1% cyclosporine A cationic emulsion in the treatment of severe dry eye disease: a multicenter randomized trial.
abstract: OBJECTIVE
  The SANSIKA study was conducted to assess the treatment effect of 0.1% cyclosporine A cationic emulsion (CsA CE) eye drops on signs and symptoms of patients with severe dry eye disease (DED).
  
  
  METHODS
  This was a multicenter, randomized, double-masked, 2-parallel-arm, 6-month phase III study with a 6-month open-label treatment safety follow-up. Patients with severe DED with corneal fluorescein staining (CFS) grade 4 on the modified Oxford scale were randomized to receive once-daily CsA CE (Ikervis®) or its vehicle.
  
  
  RESULTS
  A total of 246 patients were randomized. The proportion of patients achieving ≥2 grades improvement in CFS and a 30% improvement in symptoms (Ocular Surface Disease Index [OSDI]) by month 6 was 28.6% with CsA CE vs 23.1% with vehicle (p = 0.326) (primary endpoint). Assessment of corneal damage showed greater improvement with CsA CE over vehicle in mean adjusted CFS change from baseline to month 6 (-1.764 vs -1.418, p = 0.037). There was a reduction in ocular surface inflammation assessed by human leukocyte antigen DR expression in favor of CsA CE at month 6 (p = 0.021). The mean OSDI change from baseline was -13.6 with CsA CE and -14.1 with vehicle at month 6 (p = 0.858). The main adverse event was instillation site pain (29.2% vs 8.9% in the CsA CE and vehicle groups, respectively), and it was mostly mild.
  
  
  CONCLUSIONS
  CsA CE was well-tolerated and effective in improving corneal damage and ocular surface inflammation and confirmed the positive benefit-risk ratio of this new formulation of CsA for the treatment of severe keratitis in DED.
authors.affiliation: Department of Neuroscience, Ophthalmology Unit, University of Padua, Padua - Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Leonardi
authors.affiliation: St. Eriks Eye Hospital, Stockholm - Sweden.
authors.forename: Gysbert
authors.initials: G
authors.lastname: Van Setten
authors.affiliation: Santen SAS, Evry - France.
authors.forename: Mourad
authors.initials: M
authors.lastname: Amrane
authors.affiliation: Santen SAS, Evry - France.
authors.forename: Dahlia
authors.initials: D
authors.lastname: Ismail
authors.affiliation: Santen SAS, Evry - France.
authors.forename: Jean-Sebastien
authors.initials: JS
authors.lastname: Garrigue
authors.affiliation: Royal Victoria Infirmary, Newcastle University, Newcastle upon Tyne - UK.
authors.forename: Francisco C
authors.initials: FC
authors.lastname: Figueiredo
authors.affiliation: Quinze-Vingts National Ophthalmology Hospital, Paris - France.|UPMC University, Paris 6, Vision Institute, INSERM UMRS968, CNRS UMR7210, Paris - France.|University of Versailles Saint-Quentin en Yvelines, Versailles - France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Baudouin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016572:Cyclosporine / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D015352:Dry Eye Syndromes / Q000188:drug therapy* / Q000503:physiopathology; D004655:Emulsions; D005260:Female; D015590:Fluorophotometry; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D013666:Tears / Q000502:physiology; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D004655:Emulsions; D007166:Immunosuppressive Agents; D016572:Cyclosporine